Osteoporotic hip and vertebral fractures in the Arab region: a systematic review.

Asia is projected to account for the largest proportion of the rising burden of osteoporotic fractures worldwide. Data from the Middle East is scarce. We performed a systematic review on the epidemiology of vertebral and hip osteoporotic fractures in 22 Arab League countries, using Scopus, PubMed, and Embase. We identified 67 relevant publications, 28 on hip and 39 on vertebral fractures. The mean age of patients was 70-74 years, female to male ratio 1.2:2.1. Age-standardized incidence rates, to the UN 2010 population, were 236 to 290/100,000 for women from Kuwait and Lebanon, lower in Morocco. Risk factors for hip fractures included lower BMD or BMI, taller stature, anxiolytics, and sleeping pills. Most patients were not tested nor treated. Mortality derived from retrospective studies ranged between 10 and 20% at 1 year, and between 25 and 30% at 2-3 years. Among 39 studies on vertebral fractures, 18 described prevalence of morphometric fractures. Excluding grade 1 fractures, 13.3-20.2% of women, mean age 58-74 years, had prevalent vertebral fractures, as did 10-14% of men, mean age 62-74 years. Risk factors included age, gender, smoking, multiparity, years since menopause, low BMD, bone markers, high sclerostin, low IgF1, hypovitaminosis D, abdominal aortic calcification score, and VDR polymorphisms. Vertebral fracture incidence in women from Saudi Arabia, mean age 61, was 6.2% at 5 years, including grade 1 fractures. Prospective population-based fracture registries, prevalence studies, predictive models, fracture outcomes, and fracture liaison services from Arab countries are still lacking today. They are the pillars to closing the care gap of this morbid disease.

Disease burden of osteoporosis and other non-communicable diseases in Lebanon.

Osteoporosis is more common than most feared non-communicable diseases in the Middle East. This justifies the need to place osteoporosis as a health priority in the region. INTRODUCTION: Osteoporosis is a common disease associated with severe debilitating consequences. The objective of this study is To evaluate and compare disease burden from osteoporosis and other non-communicable diseases (NCDs) in Lebanon. METHODS: We assessed the prevalence of osteoporosis and other NCDs, such as obesity, diabetes, hypertension, dyslipidemia, and cardiovascular diseases, based on a published population-based study of Lebanese ≥ 65 years. We compared incidence rates of hip fractures and major osteoporotic fractures (MOF) (spine, hip, humerus, and forearm) to the five commonest cancers in women ≥ 50 years. Rates were based on the national hip fracture and cancer registry data, provided by the Lebanese Ministry of Public Health. MOF incidence rates were derived from national hip fracture incidence rates and MOF/hip fractures incidence rate ratios from the literature. RESULTS: Over 70% of elderly Lebanese had osteoporosis defined by densitometric criteria or prevalent morphometric vertebral fractures. This by far exceeded the prevalence of other NCDs, such as hypertension (53%), diabetes (21%), dyslipidemia (31%), and cardiovascular diseases (30%). Morphometric vertebral fractures (grades 2 and 3) were present in 19% of women and 12% of men. The incidence rates for MOF were 1.6 times greater than those for breast cancer, and 7.4-9.9 folds higher than those for the next commonest cancers of the lungs, colon, and ovaries. Hip fracture incidence rates were lower than those of breast cancer but were 2.1-2.8 folds higher than those of the above-mentioned cancers. CONCLUSION: This first of its kind study in the Middle East demonstrates that osteoporosis is a common disease, more common than most feared NCDs. Our findings are comparable to those in western populations and justify placing osteoporosis on the top of NCDs' priority list in our country and possibly the region.

Diagnosis and management of bone fragility in diabetes: an emerging challenge.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.

Hyperphosphatemic familial tumoral calcinosis secondary to fibroblast growth factor 23 (FGF23) mutation: a report of two affected families and review of the literature.

Hyperphosphatemic familial tumoral calcinosis (HFTC), secondary to fibroblast growth factor 23 (FGF23) gene mutation, is a rare genetic disorder characterized by recurrent calcified masses. We describe young Lebanese cousins presenting with HFTC, based on a retrospective chart review and a prospective case study. In addition, we present a comprehensive review on the topic, based on a literature search conducted in PubMed and Google Scholar, in 2014 and updated in December 2017. While the patients had the same previously reported FGF23 gene mutation (homozygous c.G367T variant in exon 3 leading to a missense mutation), they presented with variable severity and age of disease onset (at 4 years in patient 1 and at 23 years in patient 2). A review of the literature revealed several potential patho-physiologic pathways of HFTC clinical manifestations, some of which may be independent of hyperphosphatemia. Most available treatment options aim at reducing serum phosphate level, by stimulating renal excretion or by inhibiting intestinal absorption. HFTC is a challenging disease. While the available medical treatment has a limited and inconsistent effect on disease symptomatology, surgical resection of calcified masses remains the last resort. Research is needed to determine the safety and efficacy of FGF23 replacement or molecular therapy, targeting the specific genetic aberration. Hyperphosphatemic familial tumoral calcinosis is a rare genetic disorder characterized by recurrent calcified masses, in addition to other visceral, skeletal, and vascular manifestations. It remains a very challenging disease.

Worldwide prevalence and incidence of osteoporotic vertebral fractures.

We investigated the prevalence and incidence of vertebral fractures worldwide. We used a systematic Medline search current to 2015 and updated as per authors' libraries. A total of 62 articles of fair to good quality and comparable methods for vertebral fracture identification were considered. The prevalence of morphometric vertebral fractures in European women is highest in Scandinavia (26%) and lowest in Eastern Europe (18%). Prevalence rates in North America (NA) for White women ≥50 are 20-24%, with a White/Black ratio of 1.6. Rates in women ≥50 years in Latin America are overall lower than Europe and NA (11-19%). In Asia, rates in women above ≥65 are highest in Japan (24%), lowest in Indonesia (9%), and in the Middle East, Lebanon, rates are 20%. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Incidence data is less abundant and more heterogeneous. Age-standardized rates in studies combining hospitalized and ambulatory vertebral fractures are highest in South Korea, USA, and Hong Kong and lowest in the UK. Neither a North-South gradient nor a relation to urbanization is evident. Conversely, the incidence of hospitalized vertebral fractures in European patients ≥50 shows a North-South gradient with 3-3.7-fold variability. In the USA, rates in Whites are approximately 4-fold higher than in Blacks. Vertebral fractures variation worldwide is lower than observed with hip fractures, and some of highest rates are unexpectedly from Asia. Better quality representative studies are needed. We investigate the occurrence of vertebral fractures, worldwide, using published data current until the present. Worldwide, the variation in vertebral fractures is lower than observed for hip fractures. Some of the highest rates are from North America and unexpectedly Asia. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Better quality representative data is needed.

Impact of vitamin D replacement in adults and elderly in the Middle East and North Africa: a systematic review and meta-analysis of randomized controlled trials.

In the Middle East and North Africa (MENA), a vitamin D dose ≥2000 IU/day may be needed to allow to the majority of the population to reach the target 25-hydroxyvitamin D (25(OH)D) level ≥20 ng/ml. Data in the region on the effect of vitamin D supplementation on various skeletal and extra-skeletal effects are scarce. INTRODUCTION: Hypovitaminosis D is prevalent worldwide, more so in the Middle East and North Africa (MENA). This study aims to determine the effects of vitamin D replacement on the mean difference in 25-hydroxyvitamin D [25(OH)D] level reached and other outcomes, in the MENA. METHODS: This is a meta-analysis of randomized trials from the MENA, administering vitamin D supplementation for at least 3 months, without language or time restriction. We conducted a comprehensive search in seven databases until July 2015. We abstracted data from published reports, independently and in duplicate. We calculated the mean difference (MD) and 95 % CI of 25(OH)D level reached for eligible comparisons, and pooled data using RevMan version 5.3. RESULTS: We identified 2 studies in elderly and 17 in adults; for the latter, 11 were included in the meta-analysis. Comparing a high vitamin D dose (>2000 IU/day) to placebo (nine studies), the MD in 25(OH)D level achieved was 18.3 (CI 14.1; 22.5) ng/ml; p value < 0.001; I 2 = 92 %. Comparing an intermediate dose (800-2000 IU/day) to placebo (two studies), the MD in 25(OH)D level achieved was 14.7 (CI 4.6; 24.9) ng/ml; p value 0.004; I 2 = 91 %. Accordingly, 89 and 71 % of participants, in the high and intermediate dose groups, respectively, reached the desirable level of 20 ng/ml. The risk of bias in the included studies was unclear to high, except for three studies. CONCLUSION: In the MENA region, vitamin D doses ≥2000 IU/day may be needed to reach the target 25(OH)D level ≥20 ng/ml. The long-term safety and the efficacy of such doses on various outcomes are unknown.

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.

Effect of vitamin D replacement on maternal and neonatal outcomes: a randomised controlled trial in pregnant women with hypovitaminosis D. A protocol.

INTRODUCTION: The vitamin D recommended doses during pregnancy differ between societies. The WHO guidelines do not recommend routine prenatal supplementation, but they underscore the fact that women with the lowest levels may benefit most. The effects of routine supplementation during pregnancy on maternal and neonatal clinical outcomes have not been investigated in the Middle East, where hypovitaminosis D is prevalent. Our hypothesis is that in Middle Eastern pregnant women, a vitamin D dose of 3000 IU/day is required to reach a desirable maternal 25-hydroxyvitamin D [25(OH)D] level, and to positively impact infant bone mineral content (BMC). METHODS AND ANALYSIS: This is a multicentre blinded randomised controlled trial. Pregnant women presenting to the Obstetrics and Gynaecology clinics will be approached. Eligible women will be randomised to daily equivalent doses of cholecalciferol, 600 IU or 3000 IU, from 15 to 18 weeks gestation until delivery. Maternal 25(OH)D and chemistries will be assessed at study entry, during the third trimester and at delivery. Neonatal anthropometric variables and 25(OH)D level will be measured at birth, and bone and fat mass assessment by dual-energy X-ray absorptiometry scan at 1 month. A sample size of 280 pregnant women is needed to demonstrate a statistically significant difference in the proportion of women reaching a 25(OH)D level ≥ 50 nmol/L at delivery, and a difference in infant BMC of 6 (10)g, for a 90% power and a 2.5% level of significance. The proportions of women achieving a target 25(OH)D level will be compared between the two arms, using χ(2). An independent t test will be used to compare mean infant BMC between the two arms. The primary analysis is an intention-to-treat analysis of unadjusted results. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board at the American University of Beirut-Lebanon (IM.GEHF.22). The trial results will be published in peer-reviewed medical journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02434380.

Predictors of trabecular bone score in school children.

UNLABELLED: Trabecular bone score (TBS) is a DXA-based tool that assesses bone texture and reflects microarchitecture. It has been shown to independently predict the risk of osteoporotic fracture in the elderly. In this study, we investigated the determinants of TBS in adolescents. INTRODUCTION: TBS is a gray-level textural measurement derived from lumbar spine DXA images. It appears to be an index of bone microarchitecture that provides skeletal information additional to the standard BMD measurement and clinical risk factors. Our objectives were to characterize the relationship between TBS and both age and pubertal stages and identify other predictors in adolescents. METHODS: We assessed TBS by reanalyzing spine DXA scan images obtained from 170 boys and 168 girls, age range 10-17 years, gathered at study entry and at 1 year, using TBS software. The results are from post hoc analyses obtained using data gathered from a prospective randomized vitamin D trial. Predictors of TBS were assessed using t test or Pearson's correlation and adjusted using regression analyses, as applicable. RESULTS: The mean age of the study population was 13.2 ± 2.1 years, similar between boys and girls. Age, height, weight, sun exposure, spine BMC and BMD, body BMC and BMD, and lean and fat mass are all significantly correlated with TBS at baseline (r = 0.20-0.75, p < 0.035). Correlations mostly noted in late-pubertal stages. However, after adjustment for BMC, age remained an independent predictor only in girls. CONCLUSIONS: In univariate exploratory analyses, age and pubertal stages were determinants of TBS in adolescents. Studies to investigate predictors of TBS and to investigate its value as a prognostic tool of bone fragility in the pediatric population are needed.

Bone and mineral metabolism in patients undergoing Roux-en-Y gastric bypass.

UNLABELLED: Despite effective weight reduction, the impact of bariatric surgery on bone is a major concern. Mechanisms include decreased mechanical loading, calcium and vitamin D malabsorption, deficiency in other nutrients, and alterations in fat- and gut-derived hormones. The evidence to support clinical care pathways to prevent bone loss and fractures is at this point weak. INTRODUCTION: There is a growing concern regarding the potential deleterious impact of bariatric surgery on bone metabolism. This comprehensive review addresses this controversial topic. METHODS: We reviewed and analyzed articles evaluating bone metabolism and mechanisms for the ensuing putative bone loss in adult patients exclusively undergoing Roux-en-Y gastric bypass (RYGB) surgery, for the period spanning 1942 till September 2012. RESULTS: Mechanisms identified to contribute to alterations in bone metabolism after bypass surgery include: decreased mechanical loading, calcium and vitamin D malabsorption with secondary hyperparathyroidism, deficiency in other nutrients, in addition to alterations in adipokines, gonadal steroids, and gut-derived hormones favoring bone loss, with the exception of serotonin and glucagon-like peptide-1. The relative contribution of each of these hormones to changes in bone homeostasis after bypass surgery remains undefined. Bone loss reflected by a decline in bone mineral density (BMD) and an increase in bone turnover markers have been reported in many studies, limited for the most part by the exclusive use of dual energy X-ray absorptiometry. Well-designed long-term prospective trials with fractures as an outcome, and studies investigating the magnitude, reversibility, and impact of the observed metabolic changes on fracture outcomes are lacking. CONCLUSION: Robust conclusions regarding bone loss and fracture outcome after RYGB surgery cannot be drawn at this time. Although not evidence based, baseline evaluation and sequential monitoring with measurement of BMD and calciotropic hormones seem appropriate, with adequate calcium and vitamin D replacement. Beneficial interventions remain unclear.

Cancer-associated bone disease.

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations.

Impact of nutrition on muscle mass, strength, and performance in older adults.

Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate [corrected] relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B12 and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging.

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.

Interpretation and use of FRAX in clinical practice.

UNLABELLED: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review INTRODUCTION: The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. METHODS: This study reviews the resource documents and joint position statements of ISCD and IOF. RESULTS: Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. CONCLUSIONS: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

Effect of age, gender and calciotropic hormones on the relationship between vitamin D receptor gene polymorphisms and bone mineral density.

BACKGROUND/OBJECTIVES: Hypovitaminosis D is a major public health problem worldwide and unexpectedly more so in sunny countries. Vitamin D receptor (VDR) gene is associated with inter-individual variance in bone mineral density (BMD). Studies assessing the effect of VDR gene polymorphisms on BMD yielded conflicting results. The aim of this study was to assess the relationship between VDR polymorphisms and BMD in the Lebanese, across age groups and genders and to assess the effect of PTH and lean mass and vitamin D levels on such relationship. SUBJECTS/METHODS: In total, 203 subjects aged 65-85 years and 336 children aged 10-17 years. Polymorphisms in the VDR gene were assessed with the restriction enzymes BsmI, TaqI and ApaI. Bone mineral content, BMD and lean mass were measured using Dual-Energy X-ray Absorptiometry (DXA). The dominant hand strength was measured in children. RESULTS: Heterozygote genotype was the most frequent in both age groups. There was no difference in the frequency distribution of genotypes between the young and the elderly. No relationship between VDR genotypes and lean mass was found in either age group. Heterozygote boys had the lowest parathormone (PTH) and heterozygote elderly women had the highest BMD at the spine and forearm. CONCLUSIONS: In the Lebanese, the relationship between VDR polymorphisms and BMD differs by age. Survival does not seem to differ by VDR genotype. However, further studies are needed to assess the effect of VDR gene polymorphisms on mortality per se and time to mortality, not evaluated in this study.

Global vitamin D status and determinants of hypovitaminosis D.

UNLABELLED: This review describes the vitamin D status in different regions of the world with the objective of understanding the scope of hypovitaminosis D and the factors related to its prevalence that may contribute to the pathogenesis of osteoporosis and fragility fractures. INTRODUCTION: Vitamin D status has been linked to the pathogenesis of hip fractures as well as other skeletal and non-skeletal disorders. The purpose of this review is to provide a global perspective of vitamin D status across different regions of the world and to identify the common and significant determinants of hypovitaminosis D. METHODS: Six regions of the world were reviewed-Asia, Europe, Middle East and Africa, Latin America, North America, and Oceania-through a survey of published literature. RESULTS: The definition of vitamin D insufficiency and deficiency, as well as assay methodology for 25-hydroxyvitamin D or 25(OH)D, vary between studies. However, serum 25(OH)D levels below 75 nmol/L are prevalent in every region studied whilst levels below 25 nmol/L are most common in regions such as South Asia and the Middle East. Older age, female sex, higher latitude, winter season, darker skin pigmentation, less sunlight exposure, dietary habits, and absence of vitamin D fortification are the main factors that are significantly associated with lower 25(OH)D levels. CONCLUSION: Reports from across the world indicate that hypovitaminosis D is widespread and is re-emerging as a major health problem globally.

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.