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Biomedical subjects

R M Francis

Publications and source records attributed to R M Francis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density in healthy male subjects.

OBJECTIVE: The genetic factors determining peak bone mineral density (BMD) in men are not well characterized. Recent studies have investigated the relationship between the start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene and BMD in different populations. We have now examined the relationship between SCP of the VDR gene and BMD in a group of healthy Caucasian men from the north-east of England. SUBJECTS: Ninety-six healthy men (median age 50, range 40.0-77.0 years). MEASUREMENTS: Analysis of the FokI genotypes of SCP of the VDR and measurements of BMD at the femoral neck and lumbar spine were performed. RESULTS: FF, Ff and ff VDR FokI genotypes were found to have the highest, intermediate and the lowest lumbar spine BMD, respectively (Mean +/- SD, for FF 1.07 +/- 0.14, Ff 1.05 +/- 0.16 and ff 0.95 +/- 0.10 g/cm2). There was a significant difference in spine BMD between FF and ff genotypes (P < 0.05, analysis of variance [ANOVA]), but no such difference was apparent between Ff and ff (P > 0.05, ANOVA). Interestingly, there was no association between FokI polymorphism and femoral neck BMD (Mean +/- SD, for FF 0.85 +/- 0.12, Ff 0.87 +/- 0.15 and ff 0.83 +/- 0.15 g/cm2). The distribution of FokI VDR genotypes approached Hardy-Weinberg equilibrium and was similar to that reported for women from different ethnic groups, as the prevalence of FF and ff genotypes was 44% and 16%, respectively. CONCLUSION: The study shows that in this population of healthy men there is a weak association between lumbar spine bone mineral density and FokI restriction fragment length polymorphism at the translation initiation site of the vitamin D receptor gene.

Adult↗
PubMed2000

Male osteoporosis.

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Fractures, Bone↗
PubMed1999

Case-control study of the pathogenesis and sequelae of symptomatic vertebral fractures in men.

To investigate the pathogenesis and sequelae of symptomatic vertebral fractures (VF) in men, we have performed a case-control study, comparing 91 men with VF (median age 64 years, range 27-79 years) with 91 age-matched control subjects. Medical history, clinical examination and investigations were performed in all patients and control subjects, to identify potential causes of secondary osteoporosis, together with bone mineral density (BMD) measurements. BMD was lower at the lumbar spine and all sites in the hip in patients with VF than in control subjects (p < 0.001). Potential underlying causes of secondary osteoporosis were found in 41% of men with VF, compared with 9% of control subjects (OR 7.1; 95% CI 3.1-16.4). Oral corticosteroid and anti-convulsant treatment were both associated with a significantly increased risk of VF (OR 6.1; 95% CI 1.3-28.4). Although hypogonadism was not associated with an increased risk of fracture, the level of sex hormone binding globulin was higher (p < 0.001) and the free androgen index lower (p < 0.001) in men with VF than control subjects. Other factors associated with a significantly increased risk of VF were family history of bone disease (OR 6.1; 95% CI 1.3-28.4), current smoking (OR 2.8; 95% CI 1.2-6.7) and alcohol consumption of more than 250 g/week (OR 3.8; 95% CI 1.7-8.7). Men with VF were more likely to complain of back pain (p < 0.001) and greater loss of height (p < 0.001) than control subjects, and had poorer (p < 0.001) scores for the energy, pain, emotion, sleep and physical mobility domains of the Nottingham Health Profile. We conclude that symptomatic VF in men are associated with reduced BMD, underlying causes of secondary osteoporosis such as corticosteroid and anti-convulsant treatment, family history of bone disease, current smoking and high alcohol consumption, and that they impair the perceived health of the individual.

Adrenal Cortex Hormones↗
PubMed1999

Mitochondrial DNA deletion associated oxidative stress and severe male osteoporosis.

We have screened the mitochondrial genome of 15 men with symptomatic vertebral fractures (median age 62 years, range 27-72 years) and 17 male control subjects (median age 61 years, range 40-73 years) for the presence of mitochondrial DNA (mtDNA) deletions in peripheral monocyte DNA. Polymerase chain reaction analysis provided evidence of a common age-related (4.9 kb) mtDNA deletion situated between nucleotides 8470 and 13.460 of the genomic sequence in 5 of the 17 controls (29%) and 9 of the 15 patients (60%) investigated. Southern blotting and polymerase chain reaction revealed a novel 3.7 kb deletion in 2 patients. One of the affected patients, a 27-year-old man with severe osteoporosis (lumbar spine bone mineral density (BMD) 0.381 g/cm(2); Z-score -6.45) was found to harbor deletion in almost 50% of the mitochondria. The patient had a blood lactic acid level (4.6 nM) that was over 3 times the upper reference range (0-1.3 mM), thus confirming the presence of systemic oxidative stress. Further analysis by modified primer shift polymerase chain reaction showed the 5' breakpoint to be between the nucleotides 10.63 kb and 10.80 kb of the mtDNA. The second patient harboring the 3.7 kb deletion was older (62 years) with less severe osteoporosis (lumbar spine BMD 0.727/cm(2); Z-score -2.58) and the proportion of affected mitochondria was lower (25%). The significance of these findings is discussed and the possible relation between oxidative stress and accelerated bone loss is examined.

Adenoma, Chromophobe↗
PubMed1999

Vitamin D binding protein gene in male osteoporosis: association of plasma DBP and bone mineral density with (TAAA)(n)-Alu polymorphism in DBP.

Vitamin D binding protein (DBP) is a major carrier protein for the vitamin D metabolites, but may also play an important role in osteoclast differentiation. Polymorphisms of the DBP gene have been reported, including (TAAA)(n)-Alu repeat polymorphisms downstream of intron 8. We have examined the relationship between polymorphisms of the DBP gene and bone mineral density (BMD) and vertebral fractures in a group of 26 men with vertebral fractures but no underlying secondary cause of osteoporosis (median age 64, ages 27-72 years) and 21 male control subjects (median age 65, ages 40-77 years). There was no apparent effect of DBP phenotype on BMD, but there was a relationship between certain genotypes of (TAAA)(n)-Alu repeats and reduced BMD and vertebral fracture. Lumbar spine and femoral neck BMD were significantly lower in men with 10/8 genotype than 10/10 genotype (P < 0.05). Furthermore, the predominant genotype in men with vertebral fractures was 10/8, whereas the most common genotype in control subjects was 10/10 (odds ratio 56; 95% confidence interval 7-445). Plasma DBP was higher in men with 10/8 genotype than those with 10/10 genotype (P < 0.05), and patients with vertebral fractures were found to have higher levels than control subjects (P < 0.0005). Although our study is small because of the relative rarity of idiopathic osteoporosis in men, the results suggest that (TAAA)(n)-Alu polymorphism may have an important effect on plasma levels of DBP, bone density and fracture risk in men.

Adult↗
PubMed1999

The effects of testosterone on osteoporosis in men.

Although the pathogenesis of osteoporosis in men is multi-factorial, testosterone is known to play an important role in the maintenance of the male skeleton. This role, however, appears complicated as it may be mediated in part by aromatization to oestradiol. Testosterone replacement therapy improves bone density in men with hypogonadal osteoporosis, particularly if the epiphyses are still open. There is no well-established treatment for idiopathic osteoporosis in men, but testosterone supplementation may prove to be useful. Further studies are required to confirm the safety and efficacy of this treatment in eugonadal men with osteoporosis.

Bone Density↗
PubMed1998

Intravenous bisphosphonate prevents symptomatic osteoporotic vertebral collapse in patients after liver transplantation.

Osteoporosis is common in patients with chronic cholestatic liver disease, and atraumatic spinal fracture is a recognized complication after orthotopic liver transplantation. Bisphosphonates are potent inhibitors of osteoclast bone resorption and have been successfully used to treat postmenopausal osteoporosis. We examined whether preoperative bone mineral density can predict the risk of fracture after orthotopic liver transplantation and whether intravenous bisphosphonate can prevent fractures in high-risk patients. Beginning in February 1993, standard bone mineral density measurements of the lumbar spine were performed as part of routine pretransplantation assessment. On the basis of a preliminary analysis from January 1995, patients with a lumbar spine bone mineral density of <0.84 g/cm2, or <84% of the predicted value (age/sex), were treated with intravenous bisphosphonate (pamidronate disodium) every 3 months before and for 9 months after liver transplantation. Bone mineral density measurements were available in 90 of 136 consecutive first transplants performed in our unit from February 1993 to September 1996. Before the use of pamidronate, 7 patients sustained symptomatic vertebral fractures. Their mean spine bone mineral density was lower than in the 38 patients with no clinical evidence of fracture (81.8% +/- 12.3% v 94.2% +/- 10.2%; P = .006). Since the introduction of pamidronate, no symptomatic vertebral fractures have occurred. Of 29 surviving patients with bone mineral density <0.84 g/cm2 before transplantation, 38% who did not receive treatment with pamidronate suffered spontaneous fracture, whereas 0 of 13 who received treatment suffered such a complication. A low lumbar spine bone mineral density is associated with a high risk of symptomatic vertebral fracture after liver transplantation. These results suggest that this risk is considerably reduced by the administration of intravenous bisphosphonate before and after transplantation.

Absorptiometry, Photon↗
PubMed1998

Comparison of ultrasound measurements at the heel between adults with mental retardation and control subjects.

Little is known about the prevalence of metabolic bone disease among adults with mental retardation (now known as learning disability), although they may be at increased risk of fractures. Broadband-ultrasound attenuation (BUA) and velocity-of-sound (VOS) measurements were performed on the left heel of 170 patients in a large hospital for adults with mental retardation. For 108 of these patients, age- and gender-matched control subjects were recruited from the local community, who also underwent BUA and VOS measurements. The mean age of matched pairs of patients and control subjects was 54 (range 32-83) years for men and 53 (range 27-82) years for women. Mean +/- SEM BUA for male patients was 52 +/- 4 dB/MHz and 89 +/- 2 for control subjects, whereas for female patients it was 34 +/- 3 dB/MHz and 68 +/- 2 for control subjects. VOS was 1603 +/- 7 m/sec for male patients and 1649 +/- 5 for control subjects, and 1573 +/- 7 m/sec for female patients and 1623 +/- 5 for control subjects. All differences between patients and control subjects were significant (p < 0.005). Dual-energy X-ray absorptiometry bone mineral density (BMD) measurements were also performed in seven patients with BUA less than 50 dB/MHz, four of whom were found to have a lumbar spine or femoral neck BMD more than 2.5 SD below the mean value for young adults. This study shows that patients with mental retardation have a marked reduction in BUA and VOS measurements at the heel, compared with age-matched control subjects. There is a need to identify the major causes of low bone mass in this group, as there may be potentially avoidable risk factors for osteoporosis, such as vitamin D deficiency and hypogonadism.

Absorptiometry, Photon↗
PubMed1998

A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update.

In the UK, over 250 000 patients take continuous oral glucocorticoids (GCs), yet no more than 14% receive any therapy to prevent bone loss, a major complication of GC treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double. This review, based wherever possible on clinical evidence, aims to provide easy-to-use guidance with wide applicability. A treatment algorithm is presented for adults receiving GC doses of 7.5 mg day(-1) or more for 6 months or more. General measures, e.g. alternative GCs and routes of administration, and therapeutic interventions, e.g. cyclical etidronate and hormone replacement, are recommended.

Bone Resorption↗
PubMed1998

Management of male osteoporosis: report of the UK Consensus Group.

Although osteoporosis is generally regarded as a disease of women, up to 30% of hip fractures and 20% of vertebral fractures occur in men. Risk factors for osteoporotic fractures in men include low body mass index, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, diseases that predispose to low bone mass, and conditions increasing the risk of falls. The key drugs and diseases that definitely produce a decrease in bone mineral density (BMD) and/or an increase in fracture rate in men are long-term corticosteroid use, hypogonadism, alcoholism and transplantation. Age-related bone loss may be a result of declining renal function, vitamin D deficiency, increased parathyroid hormone levels, low serum testosterone levels, low calcium intake and absorption. Osteoporosis can be diagnosed on the basis of radiological assessments of bone mass, or clinically when it becomes symptomatic. Various biochemical markers have been related to bone loss in healthy and osteoporotic men. Their use as diagnostic tools, however, needs further investigation. A practical approach would be to consider a bone density more than one SD below the age-matched mean value (Z < -1) as an indication for therapy. The treatment options for men with osteoporosis include agents to influence bone resorption or formation and specific therapy for any underlying pathological condition. Testosterone treatment increases BMD in hypogonadal men, and is most effective in those whose epiphyses have not closed completely. Bisphosphonates are the treatment of choice in idiopathic osteoporosis, with sodium fluoride and anabolic steroids to be used as alternatives.

Adult↗
PubMed1998

Urinary free deoxypyridinoline by chemiluminescence immunoassay: analytical and clinical evaluation.

We evaluated an automated chemiluminescence immunoassay (CLIA) developed for the measurement of urinary free deoxypyridinoline (DPD). The new DPD method by CLIA is based on the competition of DPD with particle-bound pyridinoline for a limited amount of monoclonal mouse anti-DPD antibody. Total imprecision (CV) was 3.2-9.0% at 30-270 nmol/L. Regression analysis of urinary DPD concentration (second morning-void) measured by CLIA (y) and enzyme immunoassay (EIA) for adult volunteers (n = 449) with and without bone disease revealed a best fit equation of: y = 1.08 +/- 0.03x - 1.15 +/- 0.98 nmol/L (r = 0.964, S(y/x) = 14 nmol/L). CLIA and EIA methods were correlated with HPLC measurement of urinary free DPD (r = 0.846 and 0.871, respectively). For healthy adults, the creatinine-normalized excretion of DPD (mean +/- SD) measured by CLIA for 61 men (4.1 +/- 1.2 micromol DPD/mol creatinine) and 76 premenopausal women (5.3 +/- 1.8 micromol DPD/mol creatinine) did not differ significantly (P >0.05) from DPD excretion measured by EIA, and both immunoassays showed a significant gender difference (P <0.001) in reference intervals. In a clinical trial, DPD excretion (micromol DPD/mol creatinine) measured by CLIA differed substantially from the reference population for 54 untreated pagetic (12.7 +/- 8.0 SD), 255 untreated osteoporotic (7.5 +/- 4.1), 21 osteomalacic (12.4 +/- 8.5), 17 primary hyperparathyroid (9.4 +/- 4.4), and 14 secondary hyperparathyroid (9.2 +/- 5.1) patients. Clinical sensitivities of the CLIA and EIA methods range from 38% to 80% in bone disorders and limit the use of the DPD measurement in disease detection. DPD excretion after pamidronate treatment in a subgroup of the pagetic patients fell dramatically as assessed by CLIA or EIA. We conclude that the automated CLIA method for DPD is a convenient and reliable method that may aid in the evaluation and management of bone disease and is applicable to high volume testing in the routine clinical laboratory.

Adult↗
PubMed1997

Is there a differential response to alfacalcidol and vitamin D in the treatment of osteoporosis?

: There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)2D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 micro;g twice daily improved calcium absorption, decreased serum PTH, and reduced alkaline phosphatase, whereas vitamin D2 500-1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of elderly women with vertebral osteoporosis.

Female↗
PubMed1997

Osteomalacia.

Osteomalacia is a generalized bone disorder characterized by impairment of mineralization, leading to accumulation of unmineralized matrix or osteoid in the skeleton. The classical clinical features of osteomalacia include musculoskeletal pain, skeletal deformity, muscle weakness and symptomatic hypocalcaemia. In childhood the features of osteomalacia are accompanied by rickets, with widening of the epiphyses and impaired skeletal growth. The major cause of osteomalacia is vitamin D deficiency, which is most often due to reduced cutaneous production of vitamin D in housebound elderly people, immigrants to Northern countries and women who adopt strict dress codes which prohibit exposure of uncovered skin. Vitamin D deficiency osteomalacia may also occur with malabsorption, liver disease and anticonvulsant therapy. Less commonly, osteomalacia may result from abnormal vitamin D metabolism, resistance to the action of vitamin D, hypophosphataemia or toxic effects on osteoblast function.

Calcium↗