Fracture risk following bariatric surgery: a systematic review and meta-analysis.

Bariatric surgery may negatively impact bone health. We aimed to compare fracture risk following bariatric surgery by type (malabsorptive, restrictive), or to non-surgical weight loss, or to controls with obesity. We systematically searched four databases from inception until October 2020. We included observational and interventional studies on adults. We screened articles and abstracted data in duplicate and independently and assessed the risk of bias. We conducted random-effects model meta-analyses (Review Manager v5.3), to calculate the relative risk of any or site-specific fracture (CRD42019128536). We identified four trials of unclear-to-high risk of bias and 15 observational studies of fair-to-good quality. Data on fracture risk following bariatric surgery compared to medical weight loss is scarce and limited by the small number of participants. In observational studies, at a mean/median post-operative follow-up > 2 years, the relative risk of any fracture was 45% (p < 0.001) and 61% (p = 0.04) higher following malabsorptive procedures compared to obese controls and restrictive procedures, respectively, with moderate to high heterogeneity. Site-specific relative fracture risk (hip and wrist) was one- to two-folds higher post malabsorptive procedures compared to obese controls or restrictive procedures. The risks of any and of site-specific fracture were not increased following restrictive procedures compared to obese controls. Fracture risk seems to increase following malabsorptive bariatric surgeries, at a mean/median follow-up > 2 years. The risk is not increased with restrictive surgeries. The available evidence has several limitations. A prospective and rigorous long-term follow-up of patients following bariatric surgery is needed for a better assessment of their fracture risk with aging.

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.

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.

The FRAX-based Lebanese osteoporosis treatment guidelines: rationale for a hybrid model.

We describe our approach to develop FRAX-based osteoporosis treatment guidelines in Lebanon, a country with low-moderate fracture rates. A hybrid assessment algorithm that combines a fixed 10 % intervention threshold until age 70 years, and an age-dependent threshold thereafter, was deemed most suitable. INTRODUCTION: The FRAX risk calculator is used to guide intervention thresholds in several national osteoporosis guidelines. This study aimed to describe the approach in developing FRAX-based osteoporosis treatment guidelines in Lebanon, a country with relatively low fracture rates. METHODS: We reassessed previous national guidelines combined with an evaluation of age-dependent and fixed FRAX-based intervention threshold models used in the UK, the USA, and Canada. We took into consideration the risk for major osteoporotic fractures (MOF) and the proportions of subjects considered for therapy using such thresholds, before finalizing a model for Lebanon. RESULTS: The new Lebanese guidelines retained the recommendation to treat individuals with fragility fracture at the hip or spine. A femoral neck T-score ≤-2.5 in subjects without fractures was dropped, since it would imply consideration of therapy for individuals with a 10-year risk for MOF of <10 %, up to age 75 years in women. After considering the impact of both age-dependent and fixed intervention thresholds, we chose a new hybrid algorithm, combining a fixed 10 % treatment threshold until age 70 years and an age-dependent threshold thereafter. CONCLUSION: The Lebanese FRAX-based hybrid model takes into consideration the risk for MOF and the proportions of subjects considered for treatment. This model avoids consideration of drug therapy in a large proportion of younger subjects at low risk for fracture and targets high risk elderly individuals. It was deemed most suitable for Lebanon and may be an option for other countries with relatively low fracture rates.

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.

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.