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1.  Population prevalence of ultrasound features of osteoarthritis in the hand, knee and hip at age 63 years: the Newcastle thousand families birth cohort 
Musculoskeletal ultrasound has been found to be more sensitive than radiographs in detecting osteophytes. Our objective was to measure the prevalence of features of osteoarthritis (OA), in the dominant hand, knees and hips using ultrasound, within the Newcastle Thousand Families birth cohort.
Participants were aged 61–63 (mean 63) years. Knee images were scored for presence of osteophytes and effusion. Hip images were scored for the presence of osteophytes and femoral head abnormality. The first carpometacarpal joint, metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints of the index finger (dominant hand) were imaged for osteophytes.
Among 311 participants, prevalence of osteophytes at the distal interphalangeal joint was 70% while it was 23%, 10% and 41% for index proximal interphalangeal and metacarpophalangeal and thumb base carpometacarpal joints respectively. Prevalence of knee osteophytes was 30%, hip OA was 41%. Prevalence of knee effusions was 24% (right) and 20% (left). Ultrasound evidence of generalised OA (48%) and isolated hand OA (31%) was common, compared to isolated hip or knee OA (5%) and both hip and knee OA (3%).
This is the first study to assess prevalence of ultrasound features of OA in a population-based sample. The higher prevalence of hand/hip OA, when compared to previous radiographic studies, supports the hypothesis that ultrasound is more sensitive than radiography in detecting OA, particularly for osteophytes.
PMCID: PMC4031490  PMID: 24884977
Osteoarthritis; Ultrasonography; Prevalence; Epidemiology
2.  Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease 
AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis.
METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX).
RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively.
CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.
PMCID: PMC4088170  PMID: 17007022
Crohn’s disease; Osteoporosis; Osteopenia; Bone mineral density
3.  Vitamin D supplementation in older people (VDOP): Study protocol for a randomised controlled intervention trial with monthly oral dosing with 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 
Trials  2013;14:299.
The randomised, double blind intervention trial ‘Optimising Vitamin D Status in Older People’ (VDOP) will test the effect of three oral dosages of vitamin D given for one year on bone mineral density (BMD) and biochemical markers of vitamin D metabolism, bone turnover and safety in older people. VDOP is funded by Arthritis Research UK, supported through Newcastle University and MRC Human Nutrition Research and sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust.a
Vitamin D insufficiency is common in older people and may lead to secondary hyperparathyroidism, bone loss, impairment of muscle function and increased risk of falls and fractures. Vitamin D supplementation trials have yielded conflicting results with regard to decreasing rates of bone loss, falls and fractures and the optimal plasma concentration of 25 hydroxy vitamin D (25OHD) for skeletal health remains unclear.
Older (≥70 years) community dwelling men and women are recruited through General Practices in Northern England and 375 participants are randomised to take 12,000 international units (IU), 24,000 IU or 48,000 IU of vitamin D3 orally each month for one year starting in the winter or early spring. Hip BMD and anthropometry are measured at baseline and 12 months. Fasting blood samples are collected at baseline and three-month intervals for the measurement of plasma 25OHD, parathyroid hormone (PTH), biochemical markers of bone turnover and biochemistry to assess the dose–response and safety of supplementation. Questionnaire data include falls, fractures, quality of life, adverse events and outcomes, compliance, dietary calcium intake and sunshine exposure.
This is the first integrated vitamin D supplementation trial in older men and women using a range of doses given at monthly intervals to assess BMD, plasma 25OHD, PTH and biochemical markers of bone turnover and safety, quality of life and physical performance. We aim to investigate the vitamin D supplementation and plasma 25OHD concentration required to maintain bone health and to develop a set of biochemical markers that reflects the effect of vitamin D on bone. This will aid future studies investigating the effect of vitamin D supplementation on fracture risk.
#ISRCTN 35648481 (assigned 16 August 2012), EudraCT 2011-004890-10.
PMCID: PMC3848647  PMID: 24041337
Vitamin D supplementation trial; Bone mineral density; 25 hydroxy vitamin D; Parathyroid hormone; Bone markers; Older people
5.  Lack of Association of Bone Morphogenetic Protein 2 Gene Haplotypes with Bone Mineral Density, Bone Loss, or Risk of Fractures in Men 
Journal of Osteoporosis  2011;2011:243465.
Introduction. The association of bone morphogenetic protein 2 (BMP2) with BMD and risk of fracture was suggested by a recent linkage study, but subsequent studies have been contradictory. We report the results of a study of the relationship between BMP2 genotypes and BMD, annual change in BMD, and risk of fracture in male subjects. Materials and Methods. We tested three single-nucleotide polymorphisms (SNPs) across the BMP2 gene, including Ser37Ala SNP, in 342 Caucasian Englishmen, comprising 224 control and 118 osteoporotic subjects. Results. BMP2 SNP1 (Ser37Ala) genotypes were found to have similar low frequency in control subjects and men with osteoporosis. The major informative polymorphism, BMP2 SNP3 (Arg190Ser), showed no statistically significant association with weight, height, BMD, change in BMD at hip or lumbar spine, and risk of fracture. Conclusion. There were no genotypic or haplotypic effects of the BMP2 candidate gene on BMD, change in BMD, or fracture risk identified in this cohort.
PMCID: PMC3195445  PMID: 22013543
6.  Reliability and validity of ultrasound imaging of features of knee osteoarthritis in the community 
Radiographs are the main outcome measure in epidemiological studies of osteoarthritis (OA). Ultrasound imaging has unique advantages in that it involves no ionising radiation, is easy to use and visualises soft tissue structures. Our objective was to measure the inter-rater reliability and validity of ultrasound imaging in the detection of features of knee OA.
Eighteen participants from a community cohort, had both knees scanned by two trained musculoskeletal sonographers, up to six weeks apart. Inter-rater reliability for osteophytes, effusion size and cartilage thickness was calculated by estimating Kappa (κ) and Intraclass correlation coefficients (ICC), as appropriate. A measure of construct validity was determined by estimating κ between the two imaging modalities in the detection of osteophytes.
Reliability: κ for osteophyte presence was 0.77(right femur), 0.65(left femur) and 0.88 for both tibia. ICCs for effusion size were 0.70(right) and 0.85(left). Moderate to substantial agreement was found in cartilage thickness measurements. Validity: For osteophytes, κ was moderate to excellent at 0.52(right) and 0.75(left).
Substantial to excellent agreement was found between ultrasound observers for the presence of osteophytes and measurement of effusion size; it was moderate to substantial for femoral cartilage thickness. Moderate to substantial agreement was observed between ultrasound and radiographs for osteophyte presence.
PMCID: PMC3079707  PMID: 21470410
Musculoskeletal ultrasound; knee osteoarthritis; cartilage; bone; reliability; validity
7.  Skeletal Site-Related Variation in Human Trabecular Bone Transcriptome and Signaling 
PLoS ONE  2010;5(5):e10692.
The skeletal site-specific influence of multiple genes on bone morphology is recognised, but the question as to how these influences may be exerted at the molecular and cellular level has not been explored.
To address this question, we have compared global gene expression profiles of human trabecular bone from two different skeletal sites that experience vastly different degrees of mechanical loading, namely biopsies from iliac crest and lumbar spinal lamina.
Principal Findings
In the lumbar spine, compared to the iliac crest, the majority of the differentially expressed genes showed significantly increased levels of expression; 3406 transcripts were up- whilst 838 were down-regulated. Interestingly, all gene transcripts that have been recently demonstrated to be markers of osteocyte, as well as osteoblast and osteoclast-related genes, were markedly up-regulated in the spine. The transcriptome data is consistent with osteocyte numbers being almost identical at the two anatomical sites, but suggesting a relatively low osteocyte functional activity in the iliac crest. Similarly, osteoblast and osteoclast expression data suggested similar numbers of the cells, but presented with higher activity in the spine than iliac crest. This analysis has also led to the identification of expression of a number of transcripts, previously known and novel, which to our knowledge have never earlier been associated with bone growth and remodelling.
Conclusions and Significance
This study provides molecular evidence explaining anatomical and micro-architectural site-related changes in bone cell function, which is predominantly attributable to alteration in cell transcriptional activity. A number of novel signaling molecules in critical pathways, which have been hitherto not known to be expressed in bone cells of mature vertebrates, were identified.
PMCID: PMC2872667  PMID: 20502692
8.  Nutrition and bone health projects funded by the UK Food Standards Agency: have they helped to inform public health policy? 
The British journal of nutrition  2008;99(1):198-205.
The UK Food Standards Agency convened an international group of expert scientists to review the Agency-funded projects on diet and bone health in the context of developments in the field as a whole. The potential benefits of fruit and vegetables, vitamin K, early-life nutrition and vitamin D on bone health were presented and reviewed. The workshop reached two conclusions which have public health implications. First, that promoting a diet rich in fruit and vegetable intakes might be beneficial to bone health and would be very unlikely to produce adverse consequences on bone health. The mechanism(s) for any effect of fruit and vegetables remains unknown, but the results from these projects did not support the postulated acid–base balance hypothesis. Secondly, increased dietary consumption of vitamin K may contribute to bone health, possibly through its ability to increase the γ-carboxylation status of bone proteins such as osteocalcin. A supplementation trial comparing vitamin K supplementation with Ca and vitamin D showed an additional effect of vitamin K against baseline levels of bone mineral density, but the benefit was only seen at one bone site. The major research gap identified was the need to investigate vitamin D status to define deficiency, insufficiency and depletion across age and ethnic groups in relation to bone health.
PMCID: PMC2755801  PMID: 18086331
Bone; Osteoporosis; Fracture; Calcium; Vitamin D; Vitamin K; Fruit and vegetables

Results 1-9 (9)