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Biomedical subjects

D M Reid

Publications and source records attributed to D M Reid.

At least 55 records · Page 3Linked to original sources
PubMed2001

Incidence of distal forearm fracture in British men and women.

Fracture of the distal forearm is one of the most frequent osteoporotic fractures. However, there are few data concerning its incidence in Britain. The aim of this study was to determine the incidence of distal forearm fracture in adult British men and women. Six centers took part in the study: Aberdeen, Hull, Nottingham, Portsmouth, Southampton and Truro. At each center, men and women aged 35 years and over with an incident distal forearm fracture and who resided in the catchment area of the main hospital at that center, were identified during a 12 month period. Incident fractures were identified from all possible point-of-contact sources in each locality, including accident and emergency records, fracture clinics, ward listings and plaster room registers. The population at risk was defined geographically according to postcode and the denominator obtained from 1991 census data mapped to these postcodes. During the 12 month study period, 3161 individuals with distal forearm fracture were identified. The age-adjusted incidence, age 35 years and over, was 36.8/10,000 person-years in women and 9.0/10,000 person-years in men. In women, the incidence of fracture increased progressively with age from the perimenopausal period, while in men the incidence remained low until later life. Fractures were more frequently left-sided (55.6%) and 19.4% of subjects required hospitalization. On the basis of these data we estimate that 71,000 adult men and women sustain a distal forearm fracture in Britain each year. Compared with previous British surveys the pattern of incidence with age appears to have changed in women, the reason for this is unclear.

Adult↗
PubMed2001

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Aged↗
PubMed2001

Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: a prospective, population-based study in men and women.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mineral density and increased fracture risk. Although the genetic basis of osteoporosis is incompletely understood, previous studies have identified a polymorphism affecting an Sp1 binding site in the COLIA1 gene that predicts bone mineral density and osteoporotic fractures in several populations. Here we investigated the role of COLIA1 genotyping and bone densitometry in the prediction of osteoporotic fractures in a prospective, population-based study of men (n = 156) and women (n = 185) who were followed up for a mean (+/- SEM) of 4.88+/-0.03 years. There was no significant difference in bone density, rate of bone loss, body weight, height, or years since menopause between the genotype groups but women with the 'ss' genotype were significantly older than the other genotype groups (p = 0.03). Thirty-nine individuals sustained 54 fractures during follow-up and these predominantly occurred in women (45 fractures in 30 individuals). Fractures were significantly more common in females who carried the COLIA1 's' allele (p = 0.001), although there was no significant association between COLIA1 genotype and the occurrence of fractures in men. Logistic regression analysis showed that carriage of the COLIA1 's' allele was an independent predictor of fracture in women with an odds ratio (OR) [95% CI] of 2.59 [1.23-5.45], along with spine bone mineral density (OR = 1.57 [1.04-2.37] per Z-score unit) and body weight (OR = 1.05 [1.01-1.10] per kilogram). Moreover, bone densitometry and COLIA1 genotyping interacted significantly to enhance fracture prediction in women (p = 0.01), such that the incidence of fractures was 45 times higher in those with low BMD who carried the 's' allele (24.3 fractures/100 patient-years) compared with those with high BMD who were 'SS' homozygotes (0.54 fracture/100 patient-years). We conclude that in our population, COLIA1 genotyping predicts fractures independently of bone mass and interacts with bone densitometry to help identify women who are at high and low risk of sustaining osteoporotic fractures.

Absorptiometry, Photon↗
PubMed2001

Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy.

Limited information is available on the effect of bisphosphonates in men receiving corticosteroid therapy. We studied 184 men among the patients enrolled in two, double-blind, placebo-controlled, 1-year studies with similar protocols. The studies evaluated the effects of risedronate in patients beginning corticosteroid treatment at a dose of at least 7.5 mg per day of prednisone or equivalent (prevention study) or continuing long-term treatment of corticosteroid at that dose (treatment study). The men received either placebo or risedronate (2.5 mg or 5 mg) daily, along with calcium supplementation (500-1000 mg). Endpoints included differences in bone mineral density (BMD) at the lumbar spine, femoral neck, and femoral trochanter, assessment of vertebral fractures, changes in biochemical markers of bone turnover, and overall safety. In the treatment study, risedronate 5 mg significantly (P < 0.01) increased lumbar spine BMD by 4.8% at the lumbar spine, 2.1% at the femoral neck, and 2.6% at the femoral trochanter compared with baseline values. In the prevention study, bone loss was prevented with risedronate 5 mg; in the placebo group, BMD decreased significantly (P < 0.01) by 3.4%, 3.3%, and 3.4% in the lumbar spine, femoral neck, and trochanter, respectively, at 1 year. The differences between risedronate 5 mg and placebo groups were significant at all skeletal sites in the prevention study (P < 0.01) and at the lumbar spine in the treatment study (P < 0.001). The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than the 5 mg dose. When the data from the two studies were combined, the incidence of vertebral fractures decreased 82.4% (95% confidence interval, 36.6%-95.1%) in the pooled risedronate groups compared with placebo (P = 0.008). Risedronate was well tolerated in men, with a similar incidence of upper gastrointestinal adverse events in the placebo and treatment groups. Daily treatment with risedronate increases bone density and decreases vertebral fracture risk within 1 year in men receiving corticosteroid therapy.

Adolescent↗
PubMed2001

Association between COLIA1 Sp1 alleles and femoral neck geometry.

Genetic factors play an important role in the pathogenesis of osteoporosis by affecting bone mineral density and other predictors of osteoporotic fracture risk such as ultrasound properties of bone and skeletal geometry. We previously identified a polymorphism of a Sp1 binding site in the Collagen Type 1 Alpha 1 gene (COLIA1) that has been associated with reduced BMD and an increased risk of osteoporotic fractures in several populations. Here we looked for evidence of an association between COLIA1 Sp1 alleles and femoral neck geometry. The study group comprised 153 patients with hip fracture, and 183 normal subjects drawn at random from the local population. Femoral neck geometry was assessed by analysis of pelvic radiographs in the fracture patients and DXA scan printouts in the population-based subjects. The COLIA1 genotypes were detected by polymerase chain reaction and were in Hardy Weinberg equilibrium: "SS" = 222 (66%); "Ss" = 105 (31.3%); and "ss" = 9 (2.7%). There was no significant difference in hip axis length or femoral neck width between the genotype groups, but femoral neck-shaft angle was increased by about 2 degrees in the Ss/ss genotype groups (n = 114) when compared with SS homozygotes (n = 222) (P = 0.001). Previous studies have suggested that an increased femoral neck-shaft angle may increase the risk of hip fracture in the event of a sideways fall by influencing the forces that act on the femoral neck. The association COLIAI genotype and increased femoral neck angle noted here may therefore contribute to the BMD-independent increase in hip fracture risk noted in previous studies of individuals who carry the 's' allele.

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↗
PubMed2001

Defective bone formation and anabolic response to exogenous estrogen in mice with targeted disruption of endothelial nitric oxide synthase.

Nitric oxide (NO) is a pleiotropic signaling molecule that is produced by bone cells constitutively and in response to diverse stimuli such as proinflammatory cytokines, mechanical strain, and sex hormones. Endothelial nitric oxide synthase (eNOS) is the predominant NOS isoform expressed in bone, but its physiological role in regulating bone metabolism remains unclear. Here we studied various aspects of bone metabolism in female mice with targeted disruption of the eNOS gene. Mice with eNOS deficiency (eNOS KO) had reduced bone mineral density, and cortical thinning when compared with WT controls and histomorphometric analysis of bone revealed profound abnormalities of bone formation, with reduced osteoblast numbers, surfaces and mineral apposition rate. Studies in vitro showed that osteoblasts derived from eNOS KO mice had reduced rates of growth when compared with WT and were less well differentiated as reflected by lower levels of alkaline phosphatase activity. Mice with eNOS deficiency lost bone normally following ovariectomy but exhibited a significantly blunted anabolic response to high dose exogenous estrogen. We conclude that the eNOS pathway plays an essential role in regulating bone mass and bone turnover by modulating osteoblast function.

Alkaline Phosphatase↗
PubMed2001

Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom.

Genetic factors are important in the pathogenesis of osteoporosis and the estrogen receptor has been suggested as a possible candidate gene for regulation of bone mineral density (BMD). We investigated the relationship between PvuII, XbaI, and dinucleotide (TA)n repeat polymorphisms of the estrogen receptor alpha (ER-alpha) gene and BMD in a study of women from northeast Scotland in the United Kingdom. No significant association was observed between BMD values at the lumbar spine (LS) and femoral neck (FN) in relation to PvuII and XbaI polymorphisms individually, but haplotype analysis showed that BMD values (Z score) were significantly lower in those who carried the Px haplotype (n = 36) compared with those who did not (n = 170) at both the LS (mean +/- SEM; -0.775 +/- 0.125 vs. -0.285 +/- 0.082;p = 0.002) and the FN (-0.888 +/- 0.130 vs. -0.335 +/- 0.083; p = 0.0006). In keeping with this, the Px haplotype also was found to be an independent predictor of LS BMD (p = 0.019) and FN BMD (p = 0.005) in a multiple regression analysis model that included other possible predictors of BMD including age, years since menopause (YSM), hormone-replacement therapy (HRT) use, weight, and height. This model explained 15.7% and 23.4% of the total observed variance in LS and FN BMD, respectively, with the Px haplotype accounting for approximately 3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi2 = 109.8; p < 0.0001) and XbaI (chi2 = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER-alpha gene are significantly related to BMD in our population and that this association is dependent on the Px haplotype, suggesting that it is the Px haplotype, or a linked polymorphism, that confers risk.

Alleles↗
PubMed2001

COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss.

Genetic factors play an important role in the pathogenesis of osteoporosis but the genes that determine susceptibility to poor bone health are defined incompletely. Previous work has shown that a polymorphism that affects an Spl binding site in the COLIA1 gene is associated with reduced bone mineral density (BMD) and an increased risk of osteoporotic fracture in several populations. Data from cross-sectional studies have indicated that COLIA1 Sp1 alleles also may be associated with increased rates of bone loss with age, but longitudinal studies, which have examined bone loss in relation to COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 Sp1 alleles and early postmenopausal bone loss measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of 734 Scottish women who were followed up over a 5- to 7-year period. The distribution of genotypes was as expected in a white population with 484 "SS" homozygotes (65.9%); 225 "Ss" heterozygotes (30.7%), and 25 "ss" homozygotes (3.4%). Women taking hormone-replacement therapy (HRT; n = 239) had considerably reduced rates of bone loss at the spine (-0.40 +/- 0.06%/year) and hip (-0.56 +/- 0.06%/year) when compared with non-HRT users (n = 352; spine, -1.36 +/- 0.06%/year; hip, -1.21 +/- 0.05%/year; p < 0.001 for both sites). There was no significant difference in baseline BMD values at the lumbar spine (LS) or femoral neck (FN) between genotypes or in the rates of bone loss between genotypes in HRT users. However, in non-HRT users (n = 352), we found that ss homozygotes (n = 12) lost significantly more bone at the lumbar site than the other genotype groups in which ss = -2.26 +/- 0.31%/year compared with SS = -1.38 +/- 0.07%/year and Ss = -1.22 +/- 0.10%/year (p = 0.004; analysis of variance [ANOVA]) and a similar trend was observed at the FN in which ss = -1.78 +/- 0.19%/year compared with SS = -1.21 +/- 0.06%/year and Ss = -1.16 +/- 0.08%/year (p = 0.06; ANOVA). The differences in spine BMD loss remained significant after correcting for confounding factors. Stepwise multiple regression analysis showed that COLIA1 genotype independently accounted for a further 3.0% of the variation in spine BMD change after age (4.0%), weight (5.0%), and baseline BMD (2.8%). We conclude that women homozygous for the Sp1 polymorphism are at significantly increased risk of excess rates of bone loss at the spine, but this effect may be nullified by the use of HRT.

Binding Sites↗
PubMed2000

Susceptibility to osteoporotic fracture is determined by allelic variation at the Sp1 site, rather than other polymorphic sites at the COL1A1 locus.

Previous studies have identified an association between osteoporotic fracture and a polymorphism affecting a Sp1 binding site in the first intron of the collagen type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this association is direct or the result of linkage disequilibrium with other polymorphisms situated nearby. In this study we analyzed the relationship between four well-characterized single-nucleotide polymorphisms at the COL1A1 locus and osteoporotic fracture in 93 patients with vertebral fracture and 88 age-matched controls randomly selected from the community. We studied a MspI polymorphism 26 kb upstream of the COLIA1 gene, the Sp1 binding site polymorphism in intron 1, a RsaI polymorphism in intron 5 and a MnlI polymorphism in exon 52. The Sp1 and RsaI polymorphisms were in strong linkage disequilibrium (chi 2 = 77.87, p < 0.001) and weaker linkage disequilibrium was detected between the Sp1 and MnlI polymorphisms (chi 2 = 5.54, p < 0.025). There was a significant association between COL1A1 haplotypes that included the Sp1 and RsaI polymorphisms and fracture (p < 0.05-0.001), but no association with haplotypes that included only the MspI and MnlI polymorphisms. This association with fracture was strongest when haplotypes were grouped by Sp1 alleles (chi 2 = 11.15, d.f. = 1; p = 0.001). Furthermore, logistic regression analysis showed that of all the polymorphisms tested, only the Sp1 binding site polymorphism acted as an independent predictor of fracture: odds ratio [95% CI] = 2.26 [1.09-4.69]. These data suggest that it is the Sp1 polymorphism rather than other polymorphisms at the COL1A1 locus which act as a marker for osteoporotic fractures.

Absorptiometry, Photon↗
PubMed2000

Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy.

Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 +/- 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 +/- 0.4% in the placebo group (P = 0. 005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P = 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy.

Absorptiometry, Photon↗
PubMed2000

Precision of quantitative ultrasound: comparison of three commercial scanners.

Quantitative ultrasound (QUS) measurements of bone have been shown to be independent predictors of osteoporotic fracture risk. Drawbacks of this technique have included the precision of the scanners, which is said to be poorer than in dual-energy X-ray absorptiometry (DXA), in part due to difficulty in repositioning of the foot in an os calcis system and difficulty in comparison across different technologies. A new type of QUS scanner has been introduced that produces an image of the area scanned and is believed to improve precision by aiding repositioning. In this study, we compare three scanners: a dry system (McCue CUBA Clinical); a nonimaging water-bath system (Lunar Achilles(+)); and an imaging water-bath system (Osteometer DTU-One). Short-term phantom precision was calculated by repeating measurements ten times in succession on the manufacturer-supplied phantom. Long-term phantom precision was calculated by examining the phantom measurements over a 6 month period. In vivo precision was calculated in 26 normal volunteers (19 women, 7 men) and 20 women with osteoporosis. Monitoring time intervals (MTIs) were also calculated using the manufacturer's normative database. The MTI is the period between scans required to show that a "true" change has occurred, and was between 0.5 year for stiffness (a derived index produced by the Lunar Achilles instrument) and >5 years for all other measurements. The imaging system did not seem to improve precision. Precision for the QUS phantom was similar to that of DXA with a coefficient of variation (CV) of around 1.5% for BUA and <1% for speed of sound (SOS). The precision was such that the technique may be considered for monitoring skeletal changes. However, the change of bone mass at the os calcis in response to treatment was slow, which made the time needed to wait before assessing change, on the whole, longer than that for DXA. An exception may be the Lunar Achilles "stiffness" parameter, but this can only be determined in a longitudinal, comparative treatment study.

Bone Density↗
PubMed2000

Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health?

BACKGROUND: The role of nutritional influences on bone health remains largely undefined because most studies have focused attention on calcium intake. OBJECTIVE: We reported previously that intakes of nutrients found in abundance in fruit and vegetables are positively associated with bone health. We examined this finding further by considering axial and peripheral bone mass and markers of bone metabolism. DESIGN: This was a cross-sectional study of 62 healthy women aged 45-55 y. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck and by peripheral quantitative computed tomography at the ultradistal radial total, trabecular, and cortical sites. Bone resorption was calculated by measuring urinary excretion of pyridinoline and deoxypyridinoline and bone formation by measuring serum osteocalcin. Nutrient intakes were assessed by using a validated food-frequency questionnaire; other lifestyle factors were assessed by additional questions. RESULTS: After present energy intake was controlled for, higher intakes of magnesium, potassium, and alcohol were associated with higher total bone mass by Pearson correlation (P < 0.05 to P < 0.005). Femoral neck BMD was higher in women who had consumed high amounts of fruit in their childhood than in women who had consumed medium or low amounts (P < 0.01). In a regression analysis with age, weight, height, menstrual status, and dietary intake entered into the model, magnesium intake accounted for 12.3% of the variation in pyridinoline excretion and 12% of the variation in deoxypyridinoline excretion. Alcohol and potassium intakes accounted for 18.1% of the variation in total forearm bone mass. CONCLUSION: The BMD results confirm our previous work (but at peripheral bone mass sites), and our findings associating bone resorption with dietary factors provide further evidence of a positive link between fruit and vegetable consumption and bone health.

Absorptiometry, Photon↗
PubMed2000

Role of ethylene in cotyledon development of microspore-derived embryos of Brassica napus.

Ethylene production during seed development in Brassica napus occurs first at 20 d after pollination (DAP), while a second greater peak occurs at 35 DAP. Because of the inaccessible location of the embryo within the maternal tissue, microspore-derived embryos (MDEs) of B. napus were used as a model for studying the role of ethylene during embryo development. The MDEs also produced a peak in ethylene evolution at 20 DAC (i.e. the early cotyledonary stage), dropping to minimal levels by 25-30 DAC. At 20 DAC the excised cotyledon evolved 85% of the ethylene found in the whole MDE. To determine the role of ethylene, MDEs were treated with aminoethoxyvinylglycine (AVG, an inhibitor of ethylene biosynthesis), CoCl(2) (an inhibitor of 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase), and silver thiosulphate (STS, an inhibitor of ethylene action). An inhibition in ethylene production or action at 20 DAC resulted in diminished lateral cotyledon expansion, due to a reduction in the lateral expansion of cells within the cotyledon. Recovery to 'control-type' levels of cotyledon cell expansion was achieved by application of ACC (the metabolic precursor of ethylene) to AVG-treated MDEs. Thus, ethylene production at 20 DAP likely controls cotyledon expansion during embryo development.

Brassica↗
PubMed2000

Prevalence of hip fracture risk factors in women aged 70 years and over.

We estimated the prevalence of common risk factors for hip fracture and the numbers needed to treat (NNT) to prevent a hip fracture in various high-risk population groups, using a postal risk factor survey of women aged 70 years and above from General Practices in Grampian and Yorkshire. Recorded risk factors included prior fracture of any type; low body weight; smoking; and family history of fracture. The prevalence rates of hip fracture risk factors were 34%, 7% and 11% for previous fracture, maternal hip fracture and smoking, respectively for the Grampian practices (low body weight being defined as falling in the lowest quartile) and 34%, 7% and 7% for a single practice in the York area. Applying previously published estimates of risk, NNT analysis produced a value of about 300 for women with no risk factors, whilst for women with three risk factors it was between 32 and 71, depending on which risk factors were present and assuming intervention reduced fracture rates by 30% or 50%. Groups of women at high risk of hip fracture can easily be identified in primary care and offered treatment, with realistic prospects of hip fracture prevention.

Aged↗
PubMed2000

Quantitative ultrasound or clinical risk factors--which best identifies women at risk of osteoporosis?

Dual energy X-ray absorptiometry (DXA) is the current technique of choice to assess risk of future fracture and to diagnose osteoporosis as defined by bone mineral density (BMD). Guidelines for bone densitometry referral have been published listing clinical risk factors that might be considered grounds for assessment. However, these factors are known to be poorly predictive of subsequent BMD measurement and, accordingly, new inexpensive methods of selecting subjects for assessment should be sought. Quantitative ultrasound (QUS) of bone may be such a technique. Women (n = 250) considered by their general practitioners to be at risk of osteoporosis and who had been referred for DXA measurements of the spine and hip were recruited into the study. All underwent a QUS scan of the heel using a McCue CUBA Clinical machine, which measures broadband ultrasound attenuation (BUA) and velocity of sound (VOS), a clinical risk factor questionnaire, and spine and hip BMD measurement by a Norland XR-26 bone densitometer. Patients were categorized according to published diagnostic criteria for BMD, and these were also applied to the QUS parameters. Risk factors were arbitrarily categorized into "low", "medium" and "high" risk groups. Kappa scores were calculated to analyse the agreement between different techniques. Receiver operator characteristic (ROC) analyses were undertaken to demonstrate the technique with the best sensitivity and specificity for the detection of low BMD at the spine and hip. Analysis of the bone mass data demonstrated only moderate agreement (kappa 0.33) between femoral neck and spine BMD with femoral neck BMD and BUA showing a very similar level of agreement (kappa 0.31). ROC analysis demonstrated that VOS followed by BUA was the best predictor of low BMD, with risk factors alone being significantly poorer; QUS parameters are better predictors than clinical risk factors for women with low BMD and could be used effectively at the primary care level to indicate those who should be considered for full osteoporosis assessment. However, further study into the cost effectiveness of this approach is required.

Absorptiometry, Photon↗
PubMed2000

Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study.

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.

Adolescent↗