David M. Reid

Bio: David M. Reid is an academic researcher from University of Aberdeen. The author has contributed to research in topics: Osteoporosis & Bone density. The author has an hindex of 73, co-authored 245 publications receiving 15341 citations.

Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene.

Abstract: Osteoporosis is a common disease with a strong genetic component1–3, characterized by reduced bone mass and increased fracture risk4 Current evidence suggests that the inheritance of bone mass is under polygenic control5 but the genes responsible are poorly defined Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis6 In this study, we describe a novel G→T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp17 that is significantly related to bone mass and osteoporotic fracture G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss) The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 297 (95% confidence interval 163–956) for vertebral fracture in individuals who carry the ‘s’ allele While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis

A meta-analysis of the association of fracture risk and body mass index in women

Abstract: Several recent studies suggest that obesity may be a risk factor for fracture The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 22 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred Femoral neck BMD was measured in 108,267 of these women Obesity (BMI ≥ 30 kg/m(2) ) was present in 22% A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 087 (95% confidence interval [CI], 085-090) When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 116; 95% CI, 109-123) Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD At a population level, high BMI remains a protective factor for most sites of fragility fracture The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored

Genetic variants at CD28, PRDM1, and CD2/CD58 are associated with rheumatoid arthritis risk

Abstract: To discover new rheumatoid arthritis (RA) risk loci, we systematically examined 370 SNPs from 179 independent loci with P < 0.001 in a published meta-analysis of RA genome-wide association studies (GWAS) of 3,393 cases and 12,462 controls. We used Gene Relationships Across Implicated Loci (GRAIL), a computational method that applies statistical text mining to PubMed abstracts, to score these 179 loci for functional relationships to genes in 16 established RA disease loci. We identified 22 loci with a significant degree of functional connectivity. We genotyped 22 representative SNPs in an independent set of 7,957 cases and 11,958 matched controls. Three were convincingly validated: CD2-CD58 (rs11586238, P = 1 x 10(-6) replication, P = 1 x 10(-9) overall), CD28 (rs1980422, P = 5 x 10(-6) replication, P = 1 x 10(-9) overall) and PRDM1 (rs548234, P = 1 x 10(-5) replication, P = 2 x 10(-8) overall). An additional four were replicated (P < 0.0023): TAGAP (rs394581, P = 0.0002 replication, P = 4 x 10(-7) overall), PTPRC (rs10919563, P = 0.0003 replication, P = 7 x 10(-7) overall), TRAF6-RAG1 (rs540386, P = 0.0008 replication, P = 4 x 10(-6) overall) and FCGR2A (rs12746613, P = 0.0022 replication, P = 2 x 10(-5) overall). Many of these loci are also associated to other immunologic diseases.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Abstract: In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

Burden of major musculoskeletal conditions

Abstract: Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems, with indirect costs being predominant. This burden has been recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade 2000-2010. This paper describes the burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain. Osteoarthritis, which is characterized by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips, affects 9.6% of men and 18% of women aged > 60 years. Increases in life expectancy and ageing populations are expected to make osteoarthritis the fourth leading cause of disability by the year 2020. Joint replacement surgery, where available, provides effective relief. Rheumatoid arthritis is an inflammatory condition that usually affects multiple joints. It affects 0.3-1.0% of the general population and is more prevalent among women and in developed countries. Persistent inflammation leads to joint destruction, but the disease can be controlled with drugs. The incidence may be on the decline, but the increase in the number of older people in some regions makes it difficult to estimate future prevalence. Osteoporosis, which is characterized by low bone mass and microarchitectural deterioration, is a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip fracture is the most detrimental fracture, being associated with 20% mortality and 50% permanent loss in function. Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at some point in time and about 4-33% of the population at any given point. Cultural factors greatly influence the prevalence and prognosis of low back pain.

Interventions for preventing falls in older people living in the community

Abstract: As people get older, they may fall more often for a variety of reasons including problems with balance, poor vision, and dementia. Up to 30% may fall in a year. Although one in five falls may require medical attention, less than one in 10 results in a fracture. This review looked at the healthcare literature to establish which fall prevention interventions are effective for older people living in the community, and included 159 randomised controlled trials with 79,193 participants. Group and home-based exercise programmes, usually containing some balance and strength training exercises, effectively reduced falls, as did Tai Chi. Overall, exercise programmes aimed at reducing falls appear to reduce fractures. Multifactorial interventions assess an individual's risk of falling, and then carry out treatment or arrange referrals to reduce the identified risks. Overall, current evidence shows that this type of intervention reduces the number of falls in older people living in the community but not the number of people falling during follow-up. These are complex interventions, and their effectiveness may be dependent on factors yet to be determined. Interventions to improve home safety appear to be effective, especially in people at higher risk of falling and when carried out by occupational therapists. An anti-slip shoe device worn in icy conditions can also reduce falls. Taking vitamin D supplements does not appear to reduce falls in most community-dwelling older people, but may do so in those who have lower vitamin D levels in the blood before treatment. Some medications increase the risk of falling. Three trials in this review failed to reduce the number of falls by reviewing and adjusting medications. A fourth trial involving family physicians and their patients in medication review was effective in reducing falls. Gradual withdrawal of a particular type of drug for improving sleep, reducing anxiety, and treating depression (psychotropic medication) has been shown to reduce falls. Cataract surgery reduces falls in women having the operation on the first affected eye. Insertion of a pacemaker can reduce falls in people with frequent falls associated with carotid sinus hypersensitivity, a condition which causes sudden changes in heart rate and blood pressure. In people with disabling foot pain, the addition of footwear assessment, customised insoles, and foot and ankle exercises to regular podiatry reduced the number of falls but not the number of people falling. The evidence relating to the provision of educational materials alone for preventing falls is inconclusive.