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Biomedical subjects

R M Francis

Publications and source records attributed to R M Francis.

At least 19 recordsLinked to original sources
PubMed2006

Calcaneal bone mineral density in older patients who have fallen.

BACKGROUND: Annually, 35-40% of those aged >65 years fall; up to 5% of such falls result in fracture. Fracture is determined both by propensity to fall and by bone fragility. AIM: To determine osteoporosis prevalence and predictors in patients who have fallen. DESIGN: Observational cross-sectional study. METHODS: We measured calcaneal BMD in 408 consecutive patients aged >50 years attending after falling. Fall number, fracture history, weight, height, and risk factors for falls and osteoporosis were recorded. T scores (SD above or below the mean for young adults) were derived in both sexes, and Z scores (SD above or below age-related normal score) in females. RESULTS: In females (n = 300, 74%), mean (SD) T score was -1.1(1.6), and mean Z score was 0(1.4); 127 (42%) had osteoporosis (T score < - 1.6). ROC curves confirmed significant relationships between osteoporosis and age, weight and height (all p < 0.0001). Incorporating fracture history, our model (fracture aged >50 years, age >83 years, weight <57 kg, height <153 cm as dichotomous variables) predicted osteoporosis with 91% sensitivity, 34% specificity. Of 108 male fallers, 36 (33%) had osteoporosis. Age, height and weight all predicted osteoporosis (p < 0.02). The resulting model (fracture aged >50 years, age > or =80 years, weight < or =68 kg, height < or =167 cm as dichotomous variables) predicted osteoporosis with 92% sensitivity, 30% specificity. DISCUSSION: Osteoporosis prevalence is not increased in female fallers compared to age-related norms; empirical use of osteoporosis treatment solely on the basis of falls thus appears inappropriate. In both sexes, the factors predicting osteoporosis were age, height and weight. Where BMD is not practical, possible or economical, our model may be a sensitive means of predicting fallers with osteoporosis.

Absorptiometry, Photon↗
PubMed2005

Influence of IL-6, COL1A1, and VDR gene polymorphisms on bone mineral density in Crohn's disease.

BACKGROUND: Osteoporosis is an important cause of morbidity in patients with Crohn's disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis. AIM: To investigate the influence of interleukin 6 (IL-6), collagen type 1alpha1 (COL1A1), and vitamin D receptor gene (VDR) single nucleotide polymorphisms (SNP) on BMD in patients with Crohn's disease. PATIENTS: A cohort of 245 well characterised patients with Crohn's disease were recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne, and the Queen Elizabeth Hospital, Gateshead, UK. METHODS: Patients were genotyped for IL-6 C-174G SNP, COL1A1 Sp1 binding site G T SNP, VDR Taq1, and Fok1 SNPs, and CARD15 R702W, G908R, and L1007fs SNPs. BMD was measured at the lumbar spine (LSP) and hip using dual energy x ray absorptiometry. RESULTS: A total of 158 female and 87 male patients, aged 24-70 years (mean 44), were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index, pre/post-menopausal status, smoking, or steroid use. Two hundred and thirteen patients were genotyped for the IL-6 SNP. LSP and total hip BMD was significantly lower in patients with the GG genotype (48%) than the CC genotype (15%) (p = 0.041, p = 0.014). One hundred and eighty patients were genotyped for the COL1A1 SNP. There was no significant difference in BMD at LSP. Hip BMD was significantly lower in heterozygous patients compared with homozygous wild-types (p = 0.034). There were no significant differences in BMD between genotypes for the two VDR SNPs or the CARD15 genotypes examined. CONCLUSION: IL-6 and COL1A1 gene polymorphisms influence BMD in patients with Crohn's disease but the particular VDR gene polymorphisms studied do not have a major effect.

Adrenal Cortex Hormones↗
PubMed2005

Differences in bone mineral density and geometry in men and women: the Newcastle Thousand Families Study at 50 years old.

In 1947 Sir James Spence initiated the Newcastle Thousand Families study, which recruited all 1142 children born in the city between May and June that year. At the age of 50 years, 832 survivors were traced and invited to attend for measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). The aim was to compare BMD measurements of men and women in this cohort, before and after adjustment for skeletal size. The femoral neck shaft angles (NSA) were also measured manually from the DXA scan printouts. A total of 171 men and 218 women agreed to participate. As expected men had greater bone mineral content and bone area at all sites (p<0.0001) and were taller and heavier (p<0.0001) than women. Men also had significantly higher BMD than women at all regions (p<0.0002), except at the femoral neck or lumbar spine. After correction for skeletal size and body weight, men had statistically significantly lower volumetric BMD at all sites. The measurement of NSA had good intra/interobserver errors and precision (coefficient of variations 0.79%, 1.2% and 1.2%). Men had significantly larger NSAs (mean 130 degrees , range 121-138 degrees ) than women (mean 128 degrees , range 119-137 degrees ). We conclude that there are gender differences in BMD, skeletal size and geometry in middle aged men and women, which together with the subsequent rate of bone loss, may influence fracture risk in later life.

Absorptiometry, Photon↗
PubMed2004

The use of digital X-ray radiogrammetry and peripheral dual energy X-ray absorptiometry in patients attending fracture clinic after distal forearm fracture.

Despite the fact that 50% of postmenopausal women with Colles' fracture have evidence of osteoporosis, the vast majority of women with forearm fractures are neither investigated nor treated for osteoporosis. Digital X-ray radiogrammetry (DXR) provides an attractive option in patients with distal forearm fracture, as it requires no additional X-rays over and above those performed as part of clinical management. We have compared DXR analysis of nonstandardised plain films taken routinely in accident and emergency with peripheral dual energy X-ray absorptiometry (pDXA) in a group presenting with distal forearm fracture. Women presenting with a fracture of the distal forearm underwent pDXA measurements of the calcaneus. Plain X-rays performed at the time of presentation were taken to allow adequate fracture treatment. No additional radiographer training or standardisation of films was performed. The DXR technique relies upon visualisation of the metacarpal shafts and this was not visualised on 123 of 201 (61%) films. The AP plain film was thus assessed using DXR for BMD in the remaining 78 patients with a mean age of 70.6 years (SE = 1.3). Mean BMD for DXR was 0.46 g/cm2 (SE = 0.01) and for pDXA was 0.40 g/cm2 (SE = 0.01). The correlation between BMD measured using the two techniques was 0.55 (P < 0.001). Although DXR measurements could not be performed in all patients, this proportion could easily be increased by routinely including the metacarpal shaft region in X-rays obtained after suspected distal forearm fracture. The correlation between the pDXA and DXR results is comparable with those reported between DXA measurements at the forearm, spine and hip. Our study suggests that DXR may provide a feasible method for the assessment of future fracture risk. The potential advantage of DXR over calcaneal pDXA measurements is that standard forearm X-ray obtained as part of fracture management could be used.

Absorptiometry, Photon↗
PubMed2004

Acute and long-term management of patients with vertebral fractures.

Symptomatic vertebral fractures are associated with significant morbidity, excess mortality and health and social service expenditure. Up to 20% of patients with an incident vertebral fracture experience a further vertebral fracture within one year. It is therefore important that vertebral fractures are detected early, and treatment considered as soon as possible. Only a third of vertebral fractures come to medical attention, where they typically present with acute back pain, but other presentations include loss of height and increasing kyphosis. Spine X-rays should then be performed to confirm the diagnosis and exclude other pathology. Bone density measurements are not essential before starting treatment for osteoporosis in patients with low-trauma vertebral fractures, but may be useful to confirm osteoporosis when there is uncertainty about previous trauma. They may also aid in selecting the most appropriate therapy and monitoring response to treatment. Up to 30% of women and 55% of men with symptomatic vertebral crush fractures have underlying secondary osteoporosis, where treatment may lead to large increases in bone density. These conditions should therefore be sought by medical history, physical examination and appropriate investigations. The management of patients with acute vertebral fractures should include measures to reduce pain and improve mobility, as well as starting treatment for osteoporosis. Treatments have now been shown in randomized controlled trials to improve bone density and reduce the incidence of vertebral and non-vertebral fractures in patients with osteoporosis. Choice of treatment will depend on the underlying causes of bone loss, efficacy in any particular situation, cost, patient preference and the potential non-skeletal advantages and disadvantages.

Acute Disease↗
PubMed2004

Five year study of etidronate and/or calcium as prevention and treatment for osteoporosis and fractures in patients with asthma receiving long term oral and/or inhaled glucocorticoids.

BACKGROUND: Glucocorticoids are associated with a reduction in bone density and an increased risk of fracture. Concurrent treatment with bisphosphonates reduces bone loss and may prevent fractures. A randomised study was performed to determine whether treatment with cyclical etidronate and/or calcium for 5 years prevents fractures or reverses/reduces bone loss in patients receiving glucocorticoid treatment for asthma. METHODS: A multicentre, randomised, parallel group comparison of etidronate alone, calcium alone, etidronate + calcium, and no treatment, with stratification according to level of glucocorticoid exposure was carried out in 39 chest clinics in the UK. Three hundred and forty nine postmenopausal female and male outpatients with asthma aged 50-70 years were randomised. The main outcome measures were fractures and changes in bone mineral density (BMD). RESULTS: Overall, 8% of the patients experienced symptomatic fractures and 17.5% developed either a symptomatic fracture and/or a semiquantitative vertebral fracture by the end of 5 years There were no significant differences between the four treatment groups. Comparing etidronate with no etidronate, the rates of new fractures were not significantly different for symptomatic fractures (OR 1.07 (95% CI 0.46 to 2.47)) or for any fractures (OR 0.82 (95% CI 0.45 to 1.47)). For the comparison of calcium with no calcium the corresponding ORs were 1.43 (95% CI 0.62 to 3.33) and 0.91 (95% CI 0.50 to 1.63). In post hoc analysis the effect of etidronate was greater in women than in men (interaction p value 0.02) with the fracture incidence roughly halved (OR 0.39, 95% CI 0.14 to 0.99). Etidronate increased BMD at the lumbar spine by 4.1% (p = 0.001) while calcium had no significant effect. At the proximal femur the effects of treatment were not significant (relative increases etidronate 1.6%; calcium 1.1%). The rate of new fractures in patients with fractures at entry (23.7%) was higher than in those without fractures at entry (14.3%): OR 1.87 (95% CI 1.06 to 3.07). No association was found between change in BMD and new fractures. CONCLUSIONS: In patients receiving glucocorticoids for asthma etidronate significantly increased BMD over 5 years at the lumbar spine but not at the hip and had little if any protective effect against fractures, except possibly in postmenopausal women. The effects of calcium were not significant. Combination treatment had no advantage but increased unwanted effects.

Administration, Inhalation↗
PubMed2003

A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn's disease.

BACKGROUND: Osteoporosis is a common complication of Crohn's disease. AIM: To study the effect on the bone mineral density of a bisphosphonate (pamidronate) given intravenously, in combination with oral calcium and vitamin D supplements, compared with oral calcium and vitamin D supplements alone. METHODS: Seventy-four patients with Crohn's disease and low bone mineral density at the lumbar spine and/or hip were randomized to receive either a daily dose of 500 mg of calcium with 400 IU of vitamin D alone or in combination with four three-monthly infusions of 30 mg of intravenous pamidronate over the course of 12 months. The main outcome measure was the change in bone mineral density at the lumbar spine and hip, measured by dual X-ray absorptiometry, at baseline and 12 months. RESULTS: Both groups gained bone mineral density at the lumbar spine and hip after 12 months. There were significant (P < 0.05) changes in the pamidronate group, with gains of + 2.6%[95% confidence interval (CI), 1.4-3.0] at the spine and + 1.6% (95% CI, 0.6-2.5) at the hip, compared with gains of + 1.6% (95% CI, - 0.1-3.2) and + 0.9% (95% CI, - 0.4-2.1) at the spine and hip, respectively, in the group taking vitamin D and calcium supplements alone. CONCLUSIONS: In patients with Crohn's disease and low bone mineral density, intravenous pamidronate significantly increases the bone mineral density at the lumbar spine and hip.

Administration, Oral↗
PubMed2002

Mutational and polymorphic analysis of the estradiol receptor-alpha gene in men with symptomatic vertebral fractures.

In view of the importance of estrogens in the maintenance of the skeleton in men, we have carried out mutational analysis of all the exons of the estrogen-receptor-alpha (ER-alpha) gene in 64 men (36 patients with symptomatic vertebral crush fractures and 28 control subjects). Initial screening of the ER-alpha gene, carried out by single-strand conformation polymorphism analysis followed by sequencing, showed conservative mutations in exon 4 which resulted in a single base substitutions producing GGG-->GGC transition in codon 274. We also carried out polymorphic analysis of the ER-alpha gene at the PvuII restriction site in 82 men with a range of bone density measurements (53 with symptomatic vertebral fractures and 29 controls). The frequencies of PP, Pp, and pp genotypes were 20.7%, 48.8%, and 30.5%, respectively. The distribution of the alleles was similar in the patients with symptomatic vertebral crush fractures and male control subjects. There was no association between ER-alpha genotypes and bone mineral density or arthropometric parameters. This relatively small study suggests that mutations in the ER-alpha gene are unlikely to be a common cause of osteoporosis in men with vertebral fractures. Furthermore, polymorphic variation of the ER-alpha gene appears to have little effect on the pathogenesis of osteoporosis in men.

Adult↗
PubMed2002

Osteoporosis.

Osteoporosis is characterised by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. It is a common condition affecting one in three women and one in 12 men, resulting in substantial morbidity, excess mortality, and health and social services expenditure. It is therefore important to develop strategies to prevent and treat osteoporosis in both men and women. This paper reviews the pathogenesis of primary and secondary osteoporosis, as well as diagnosis, investigation, and management. This should include lifestyle changes to reduce bone loss and decrease the risk of falls, the identification and treatment of secondary causes of bone loss, and specific treatment for osteoporosis. Hormone replacement therapy, raloxifene, bisphosphonates, calcium and vitamin D, calcitonin, and parathyroid hormone have all been shown to improve bone density and decrease the risk of fracture in specific situations. It is important that treatment is tailored to the individual patient, to ensure compliance and optimise the potential benefits.

Accidental Falls↗
PubMed2001

Androgen replacement in aging men.

Serum testosterone and estradiol decline with advancing age in men, but the contribution of these changes to age-related bone loss remains unclear. Most studies show a closer relationship between bone density and serum estradiol than with serum testosterone. Nevertheless, hypogonadism is widely considered to be an important cause of male osteoporosis, occurring in up to 20% of men with vertebral fractures and 50% with hip fractures. Bone loss in hypogonadal men has been attributed to androgen and estrogen deficiency, low 1,25 dihydroxyvitamin D concentrations, malabsorption of calcium, and reduced circulating calcitonin. These abnormalities are corrected by testosterone replacement, which also decreases bone resorption and stimulates bone mineralization. Long-term testosterone replacement increases spine bone density by over 25%, although much of the improvement occurs in the first few years of treatment. There appears to be an inverse relationship between the basal serum testosterone and the increase in bone density observed with testosterone treatment, such that little change is seen in men with normal basal concentration. In contrast, an observational study in eugonadal men with vertebral fractures showed an increase in spine bone density of 5% after 6 months' treatment with testosterone, probably mediated by an increase in serum estradiol and a reduction in bone resorption. Although testosterone has beneficial effects on the skeleton, there may be adverse effects on the prostate and cardiovascular risk factors. Further studies are required to confirm the safety and efficacy of testosterone replacement in hypogonadal and eugonadal men with osteoporosis.

Aging↗
PubMed2001

Osteoporosis in men.

Osteoporosis is characterized by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Although osteoporosis is generally considered to be a condition affecting post-menopausal women, it is now clear that substantial bone loss occurs with advancing age in men, such that up to 20% of symptomatic vertebral fractures and 30% of hip fractures occur in men. This chapter highlights the incidence and prevalence of osteoporotic fractures in men and reviews the associated morbidity, excess mortality and health and social service expenditure. The determinants of peak bone mass and bone loss in men are discussed, as is the pathogenesis of osteoporosis and vertebral and hip fractures. The criteria for the diagnosis of osteoporosis in men are reviewed, together with the most appropriate investigations for secondary osteoporosis. The management of osteoporosis in men is also discussed, highlighting the most appropriate treatment options.

Aged↗
PubMed2001

Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action?

The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

Accidental Falls↗