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Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 73 records · Page 4Linked to original sources
PubMed2000

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

Age Factors↗
PubMed2000

A novel mechanism for induction of increased cortical porosity in cases of intracapsular hip fracture.

It has been suggested that, in hip fracture, the cortex on the inferoanterior (IA) to superoposterior (SP) axis is thinned and shows increased porosity. This is dependent on the presence of giant canals (i.e., diameter >385 microm), which are related to clusters of remodeling osteons. To investigate further the relationship between remodeling and bone loss, osteonal diameter (On.Dm), wall thickness (W.Th), osteoid width (O.Wi), and extent (OS) were measured in femoral neck biopsies from 12 female intracapsular hip fracture cases and 11 age- and gender-matched controls. Over 83% of giant canals were "composite" osteonal systems in which a single canal was surrounded by multiple packets of osteonal bone. Among smaller canals, over 80% of systems had a canal encircled by a single cement line containing one packet of bone ("simple"). Composites were nearly twice as prevalent in fractures (fracture cases 9.8 +/- 0.7/25 mm(2), controls 5.3 +/- 0.4/25 mm(2), p < 0. 0001), and were dependent (R(2) = 0.52) on femoral neck region (p = 0.0008) and the regional distribution of clusters of remodeling osteons (p = 0.0045). Both the inferior (I) and anterior (A) regions had an elevated number of composites (I: 263% of control values, p = 0.0054; A: 202% of control values, p = 0.0092). On.Dm was similar in fracture cases and controls (simple: fracture cases 183 +/- 3 microm, controls 191 +/- 4 microm; composites: fracture cases 446 +/- 13 microm, controls 460 +/- 13 microm). W.Th in simples was similar in fracture cases and controls (fracture cases 51 +/- 0.8 microm, controls 49 +/- 0.7 microm), but composites had significantly (p < 0. 0001) thinner walls, with the reduction in fracture cases (31%) being twice that of controls (12%, p < 0.0001). There were no differences in O.Wi. It was unusual for osteoid to fully surround the composite canal surface; OS was 38% lower in composite than simple canals (p < 0.0001). This study indicates that, in the femoral neck cortex, the principal remodeling deficit in hip fracture is specific to composite osteons. Hip fracture cases had zonal increases in composite osteon density with reduced bone formation. The data suggest that generation of composite osteons is a plausible mechanism leading to increasing porosity and trabecularization of the cortex, thus weakening the cortex in regions maximally loaded on fall impact.

Aged↗
PubMed2000

Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading.

The aim of this 1-year prospective study of acute stroke patients was to determine the effects of walking and asymmetrical weight bearing on the loss of bone mineral in the upper and lower femoral neck. Forty patients were followed. Eight remained unable to walk, whereas 32 relearned to walk independently within 7 months (12 shortly after the stroke, 15 by 2 months, 5 by 7 months). Bone mineral density (BMD) was measured in the proximal femur within the first week after stroke and 1 year later; regional BMD changes were computed for the lower and upper femoral neck. The lower part of the femoral neck is mainly influenced by compressive stresses of the hip, the upper part by tensile stresses during walking. When comparing mean BMD loss in groups of patients according to when they relearned to walk, a statistically significant trend in BMD loss was found in the lower femoral neck on both the paretic and nonparetic sides (p < 0.01 and p = 0.01, respectively), whereas, for the upper femoral neck, no significant trend was seen (p >/= 0.1). In addition, the body weight distribution during standing was assessed by use of a force-plate in 38 patients who could stand independently at the 7 month evaluation. The only significant correlation between changes in BMD and asymmetrical weight bearing was found in the lower femoral neck on the paretic side (r = 0.6, p < 0.001). In conclusion, this study shows that the reduction in BMD in the femoral neck occurs mainly in the lower part of the neck and on the paretic side. The BMD loss depended on when or if the patients relearned to walk, but also on the amount of body weight born on the paretic leg. Thus, measuring the lower part of the femoral neck gives a better estimate of the impact of gait and weight bearing than measuring the total femoral neck.

Absorptiometry, Photon↗
PubMed2000

Spatial clustering of remodeling osteons in the femoral neck cortex: a cause of weakness in hip fracture?

Intracapsular femoral neck fractures are associated with decreased cortical width and increased proportions of Haversian canals with diameters greater than the normal mean plus 3 SD (i.e., >385 microm). Such canals might be formed if closely associated resorbing osteons merge; a cortical event analogous with the loss of cancellous connectivity. To test this, we investigated the pattern of osteon distribution in the aging femoral neck to determine if remodeling osteons were distributed in anatomical clusters. Femoral neck biopsies from female patients with intracapsular hip fractures (n = 13) were compared with age/gender-matched cadaveric controls (n = 13). Solochrome-stained sections were analyzed for Haversian canal location, canal diameter, and the presence of an osteoid surface. Clustering was investigated using statistical software with a cluster defined as two or more osteoid-bearing osteon centers within 0.75 mm of each other. Clusters occurred more frequently than would be expected by chance (p < 0.001). Fracture cases had more clusters per unit area (3.14 +/- 0.31 clusters/25 mm2 of cortical bone) than controls (1.89 +/- 0.22) (p = 0.002). In fracture cases, the antero-inferior, antero-superior, and infero-anterior regions had more clusters per 25 mm2 than comparable control regions (ant/inf: 4.12 +/- 0.79, 1.70 +/- 0.60,p = 0.025; ant/sup: 5.31 +/- 1.1, 1.80 +/- 0.59,p = 0.013; inf/ant: 3.15 +/- 0.49, 1.27 +/-0.29, p = 0.004). The mean number of clusters per 25 mm2 per region correlated with the mean porosity per region (adjusted r2 = 0.60;p = 0.014), and the total number of giant canals per region correlated with the total number of clusters per region (adjusted r2 = 0.58; p = 0.011). In conclusion, remodeling osteons are clustered or grouped anatomically, and fracture cases have more clusters than controls. Our data suggest that merging of adjacent, clustered osteons during resorption could lead to the rapid development of canals with excessive diameters and focal weakness. Clustering is greatest in those regions that we have previously shown to have the largest relative reductions in bone strength compared with controls and known to be maximally loaded during a sideways fall. This implicates the remodeling process underlying clustering of remodeling osteons in the aetiology of hip fracture.

Aged↗
PubMed2000

Bcl-2, tissue transglutaminase and p53 protein expression in the apoptotic cascade in ribs of premature infants.

Apoptotic cells of the human growth plate have not previously been demonstrated in situ. We have investigated the distribution of apoptotic cells in costosternal growth plates and bone of premature infants aged 4-11 d with a gestational age of approximately 26 wk. In addition, we investigated the immunolocalisation of apoptosis-related proteins within the growth plates and associated bone. A proportion of late hypertrophic chondrocytes and osteocytes within newly formed primary spongiosa showed evidence of highly fragmented DNA. The incidence of osteocyte apoptosis decreased as the distance from the chondroosseous junction increased. Tissue transglutaminase (tTG) expression was associated with apoptosis of osteocytes and hypertrophic chondrocytes. In contrast the presence of tTG was demonstrated in osteoblasts and bone lining cells but it did not colocalise with evidence of apoptosis. The anti-apoptotic gene product Bcl-2 was absent from the growth plate but was present in osteocytes. Visual assessment indicated a greater occurrence of the protein in cells occupying regions of low apoptosis. P53 was not demonstrated in the growth plate or bone. These findings would indicate that human growth plate chondrocytes appear to show little provision for ensuring cell longevity. In contrast osteocyte apoptosis appears negatively correlated with the skeletal distribution of Bcl-2 protein in the human infant, implying a potential selective vulnerability in individual cells. Lack of Bcl-2 and the high incidence of osteocyte apoptosis in the more rapidly remodelling bone of the human infant suggest a potential role of osteocyte apoptosis in the remodelling process.

Apoptosis↗
PubMed2000

Phylogenetic analysis of 18 thermophilic Methanobacterium isolates supports the proposals to create a new genus, Methanothermobacter gen. nov., and to reclassify several isolates in three species, Methanothermobacter thermautotrophicus comb. nov., Methanothermobacter wolfeii comb. nov., and Methanothermobacter marburgensis sp. nov.

Using a combination of 16S rRNA analysis and antigenic fingerprinting consisting of new and published data, the phylogenetic position of 18 thermophilic isolates currently classified as Methanobacterium species was reinvestigated. The results were verified by independent methods, including, where applicable, plasmid and phage typing. Comparative analysis of 16S rRNA data for 30 strains belonging to the order Methanobacteriales strongly suggested that mesophilic and thermophilic Methanobacterium isolates are distantly related and should be assigned to separate genera. For the thermophilic strains the genus Methanothermobacter was initially proposed by Boone, Whitman and Rouvière. Furthermore, the results support a reclassification of 15 isolates in three species within the proposed genus: (i) Methanothermobacter thermautotrophicus comb. nov., containing eight isolates, six of which are able to utilize formate (type strain deltaHT); (ii) Methanothermobacter wolfeii comb. nov., containing four formate-utilizing isolates (type strain DSM 2970T); (iii) Methanothermobacter marburgensis sp. nov., containing three obligately autotrophic isolates (type strain MarburgT). Of the nine isolates formerly referred to as Methanobacterium thermoformicicum, six were reclassified as Methanothermobacter thermautotrophicus and three as Methanothermobacter wolfeii.

Antigens, Archaeal↗
PubMed2000

Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation.

BACKGROUND: Substantial evidence implicates the neuropeptide substance P (SP) in mucosal immunoinflammatory responses. Autoradiographic studies have suggested a disturbance in SP receptor expression in inflammatory bowel disease (IBD). AIMS: Because of technical limitations such as poor cellular resolution with autoradiography, we used molecular methods to specifically localise the cellular expression of the neurokinin-1 receptor (NK-1R) in IBD colon, and to quantitate NK-1R mRNA expression levels therein. METHODS: In situ hybridisation and immunohistochemistry were used to localise NK-1R mRNA and protein, respectively, in normal, ulcerative colitis (UC), and Crohn's disease (CD) colonic resections. NK-1R mRNA expression levels of normal, UC, and CD mucosal biopsies were quantitated by competitive reverse transcription-polymerase chain reaction. RESULTS: NK-1R expression was localised to lamina propria mononuclear cells, epithelium, submucosal vasculature, smooth muscle, and myenteric plexus of normal and IBD colon. No ectopic NK-1R expression was observed in IBD. However, we found increased numbers of NK-1R expressing lymphoid cells in IBD tissue, aberrant negative epithelial expression of NK-1R in UC, and increased expression of NK-1R in CD myenteric plexus. Quantitation of NK-1R mRNA expression in IBD colonic mucosal biopsies revealed marked upregulation of NK-1R mRNA levels compared with non-inflamed mucosal expression levels (p<0.01). CONCLUSIONS: This report demonstrates the strategic localisation and upregulation of NK-1R expression in IBD colon, and thereby suggests the involvement of substance P in the pathophysiological symptoms of IBD.

Adult↗
PubMed2000

Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis.

OBJECTIVE: To determine whether growth hormone (rhGH) affects bone mineral metabolism and bone mineral content (BMC, g/cm) in a therapeutic trial of recombinant growth hormone in growth retarded children with juvenile chronic arthritis (JCA) treated with steroid. METHODS: BMC was measured in 20 children (of whom 17 were treated with corticosteroid) before and after one year of rhGH. Children were randomized to receive either low dose (12 IU/m2/week) or high dose (24 IU/m2/week) for one year. Three monthly assessments were made of disease activity and anthropomorphic measurements. Blood and urine samples were also obtained to measure indicators of disease activity, bone remodeling, and vitamin D and parathyroid hormone (PTH) status. RESULTS: BMC increased during the treatment period and correlated with increasing height. Osteocalcin levels, normally indicators of bone formation, increased after rhGH treatment and correlated significantly with height velocity, particularly for the high dose treatment group. In contrast, osteocalcin levels were negatively correlated with C-reactive protein levels, both before and during treatment. Height velocity, vitamin D, PTH, and osteocalcin levels were significantly lower than age matched controls before treatment. CONCLUSION: Steroid treated children with both JCA and severe growth retardation have reduced vitamin D, PTH, and osteocalcin levels. After treatment with rhGH, height velocity increased, as did BMC. Growth hormone might be a useful adjunct in the treatment of severe growth retardation and osteoporosis in children with JCA. The longterm benefits of rhGH in the treatment of osteoporosis remain unclear.

Adolescent↗
PubMed1999

Does the presence of postmenopausal symptoms influence susceptibility to vertebral deformity? European Vertebral Osteoporosis Study (EVOS) Group.

BACKGROUND: Previous reports suggest a possible increased risk of osteoporosis in those with postmenopausal symptoms. There are, however, no data from population samples, exploring the relationship between postmenopausal symptoms and vertebral osteoporosis. AIM: To determine if there is an association between self-reported postmenopausal symptoms and radiographic vertebral deformity. METHODS: Women aged 50 years and over were recruited from population registers in 30 European centres and invited to attend for an interviewer administered questionnaire and lateral thoracic and lumbar spine radiographs. The questionnaire sought information about aspects of lifestyle, personal, medical and gynaecological history, including postmenopausal symptoms: flushing, sleep disturbance and 'other' symptoms. Radiographs were taken according to a standard protocol and evaluated morphometrically. Vertebral deformity was defined according to the McCloskey-Kanis method. Bone mineral density data were obtained in a subsample of women at both the spine and femoral neck. RESULTS: A total of 4023 postmenopausal women, aged 50-64 years, were studied: 73% reported a history of flushing, 45% sleep disturbance and 23% 'other' symptoms, at or around their menopause. The prevalence of vertebral deformity was 8.2%. Those with postmenopausal symptoms were slightly younger and more likely to have ever taken hormone replacement therapy (HRT) than those without symptoms. After adjusting for potential confounders (age, centre, body mass index, cigarette smoking and HRT) there was no association between deformity and any of the postmenopausal symptoms: flushing (odds ratio (OR) 1.0; 95% confidence intervals (CI) 0.8, 1.3), sleep disturbance (OR 1.0; 95% CI 0.8, 1.2), 'other' symptoms (OR 0.9; 95% CI 0.7, 1.3). Amongst women who had ever taken HRT, however, those with vertebral deformity were more likely to report a history of flushing (OR 2.1; 95% CI 0.9,4.8). CONCLUSION: A history of postmenopausal symptoms per se does not appear to be associated with increased susceptibility to vertebral osteoporosis. However, women with more severe symptoms (as suggested by their use of HRT) may be at increased risk.

Bone Density↗
PubMed1999

Quality of life in patients with vertebral fractures: validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Working Party for Quality of Life of the European Foundation for Osteoporosis.

Vertebral fractures may be minor or lead to pain, decreased physical function, immobility, social isolation and depression, which together contribute to quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with vertebral fractures. This questionnaire, QUALEFFO, includes questions in the domains pain, physical function, social function, general health perception and mental function. QUALEFFO was validated in a multicenter study in seven countries. The study was done in 159 patients aged 55-80 years with clinical osteoporosis, i.e., back pain and other complaints with at least one vertebral fracture and lumbar bone mineral density T-score <-1. Patients with a recent vertebral fracture were excluded because of unstable disease. Controls were age- and sex-matched, and did not have chronic back pain or vertebral fractures. Subjects with conditions exerting a major influence on quality of life were excluded. The QUALEFFO was administered twice within 4 weeks and compared with a generic questionnaire, the Short Form 36 of the Medical Outcomes Study (SF-36). Standard spinal radiographs were made for assessment of vertebral height. Seven questions were removed from the analysis because of low response rate, linguistic ambiguities or redundancy. The 41 remaining questions were analyzed for repeatability, internal consistency and the capacity to discriminate between patients with vertebral fractures and controls. Comparison with the SF-36 was performed within similar domains by conditional logistic regression and by receiver operating characteristic (ROC) curves. The repeatability of QUALEFFO was good (kappa statistics 0.54-0.90) and 26 of 41 questions had a kappa score >/=0.70. The internal consistency of the five domains was adequate, with Crohnbach alpha around 0.80. All except five questions discriminated significantly between patients and controls. The median scores of QUALEFFO were significantly higher in patients with vertebral fractures than in controls in all five domain (p<0. 001), which is consistent with decreased quality of life in patients with osteoporosis. Spinal radiographs were assessed using the McCloskey-Kanis algorithm. According to this, 124 patients (78%) had vertebral fractures of >/=3 SD severity, in contrast with 7 controls (4%). Significant correlations existed between scores of similar domains of QUALEFFO and the SF-36, especially for pain, physical function and mental function. All five domains within each questionnaire discriminated significantly between fracture cases and controls. The odds ratios for pain and social function were greater for QUALEFFO, while general health perception was more discriminating using the SF-36. The ROC curve analysis of QUALEFFO indicated that all five domains were significantly predictive of vertebral fractures. When comparing similar domains of the two questionnaires, QUALEFFO domains demonstrated significantly better performance for pain, physical function and social function. The QUALEFFO total score and SF-36 physical composite score showed similar performance. In conclusion, QUALEFFO is repeatable, coherent and discriminates well between patients with vertebral fractures and control subjects. The results of this study confirm the decreased quality of life in patients with vertebral fractures.

Aged↗
PubMed1999

Intracapsular hip fracture: increased cortical remodeling in the thinned and porous anterior region of the femoral neck.

It has been shown previously that the antero-inferior cortex is subjected to maximal tensile stress during a fall onto the greater trochanter. We have recently shown that in cases of femoral neck fracture, cortical thinning and porosity is greatest in the anterior and antero-inferior region of the femoral neck. To investigate whether this is due to increased remodeling, we have quantified surface-based parameters associated with Haversian remodeling in femoral neck biopsies from women with intracapsular hip fracture and post-mortem controls. Cryostat sections of chilled biopsies were reacted for either tartrate-resistant acid phosphatase (TRAP) or alkaline phosphatase (ALP) activity. Proportions of active canals were determined in each quadrant (inferior, anterior, superior, posterior) of the femoral neck. The biopsies were then embedded in methacrylate to permit histomorphometry using Goldner's and Solochrome sections. In the cases there was no significant increase in the proportion of canals undergoing remodeling in the cortex as a whole (p = 0.846), but the regional distribution of remodeling was markedly different from that in the controls. In the anterior cortex, the proportion of canals undergoing remodeling was increased by 56% (p = 0.0087); in contrast there was a relative decrease of 35% in the superior region (p = 0.0047). In the anterior cortex of cases there were 76% and 42% increases in the proportions of eroded (p = 0.019) and osteoid-bearing (p = 0.041) canals, respectively. In the superior region, the decrease in the proportion of remodeling sites was due to a marked decrease in canals with an osteoid surface (51%; p = 0.0031). Covariance analysis with cortical porosity as the dependent variable showed that porosity was significantly dependent on the regional distribution of eroded (p = 0.033) but not on the distribution of forming (p = 0.153) canals (R(2)adj = 0.51). Cellular levels of TRAP and ALP were significantly elevated in the anterior region of cases compared with the controls (TRAP 55%, p = 0.006; ALP 36%, p = 0.003). For the posterior and inferior regions there were no marked differences in cellular TRAP and ALP levels compared with control values. These data show that the increased cortical thinning and increased porosity we have previously observed in the anterior cortex in cases of hip fracture are associated with increased indices of Haversian remodeling. These findings are consistent with the hypothesis that, in cases of hip fracture, remodeling imbalance in the anterior cortex is a continuing process up to the time of fracture and is due to increased osteoclastic cellular activity associated with an osteoblastic response that is inadequate to prevent bone loss.

Acid Phosphatase↗
PubMed1999

Treatment of reduced bone mineral density in athletic amenorrhea: a pilot study.

There is considerable concern about the adverse effects on the skeleton of loss of menstrual function as a result of athletic activity, as well as uncertainty as to how it should be managed clinically. In a pilot intervention study 34 elite middle and long-distance runners, aged 18-35 years, with menstrual irregularity due to their athletic activity were randomized to three groups: (A) to receive hormone replacement therapy (HRT) and 1000 mg calcium per day (n = 10), (B) to receive 1000 mg calcium per day (n = 14), (C) a control group who received no treatment (n = 10). Bone mineral density (BMD) was measured in the left hip and lumbar spine (L2-4) using dual-energy X-ray absorptiometry. Results were first analyzed according to whether menstruation returned, either naturally or secondary to HRT (EU), and compared with those from subjects who remained amenorrheic (AM). During the first year BMD increased in the EU group in Ward's triangle (3.8%) and the lumbar spine (4.1%; both P < 0.05). BMD fell in the AM group in all regions and the between-group differences were 5.6% (p < 0.02) in Ward's triangle, 5.8% (p < 0.02) in L2-4 and 3.9% in the trochanter (p < 0.05). An 'intention to treat' analysis was then performed. It was found that the mean relative improvement at 1 year in spinal BMD was only 1.5%, due to return of menses in some of the controls and withdrawals from treatment in the treatment group. In consequence, a trial designed to show, with 80% power and 5% significance, a measurable benefit in lumbar spine BMD resulting from allocation to HRT treatment would require about 1150 athletes with amenorrhea or oligomenorrhea. These numbers could be reduced substantially to 380 subjects by confining the trial to completely amenorrheic athletes, who in this study were less likely to regain menses. For these and other logistical reasons, an HRT trial in amenorrheic athletes could only be successfully organized through international collaboration. This study illustrates the major effects of treatment withdrawals and instability of menstrual status on the design of longitudinal studies on the bony effects of menstrual dysfunction prior to menopause.

Absorptiometry, Photon↗
PubMed1999

Bone density reduction in various measurement sites in men and women with osteoporotic fractures of spine and hip: the European quantitation of osteoporosis study.

We have measured bone mineral density (BMD) using dual X-ray absorptiometry (DXA) of the spine and hip, spinal quantitative computed tomography (QCTspi), and peripheral radial quantitative computed tomography (pQCTrad) in 334 spine and 51 hip fracture patients. The standardized hip and spine BMD for each patient was calculated and compared with the combined reference ranges published previously, each densitometer having been cross-calibrated with the prototype European Spine Phantom (ESPp) or the European Forearm Phantom (EFP). Male and female fracture cases had similar BMD values after adjusting for body size, where appropriate. This suggests that the relationship between bone density (mass per unit volume) and fracture risk is similar between men and women. However, compared with age-matched controls, mean decreases in BMD ranged from 0.78 SD units (women with hip fracture, DXAspi) to 2.57 SD units (men with spine fractures, QCTspi). The proportion of spine and hip fracture patients falling below the cutoff for osteoporosis (T-score <-2.5 SD) proposed by the World Health Organization (WHO) study group varied according to different BMD measurement procedures (range 18-94%). This finding suggests that the WHO definition requires different thresholds when used with non-DXA BMD measurement techniques. Receiver operator characteristic (ROC) analysis was used to compare measurement techniques for their ability to discriminate between cases and controls. Among DXA sites, the proximal femur was preferred when evaluating generalized bone loss, particularly in elderly people. An additional spinal BMD measurement may add clinical value if spine fracture risk assessment has a high priority. Both axial and peripheral QCT techniques performed comparably to DXA in spinal osteoporosis, so investigators and clinicians may use any of the three technologies with similar degrees of confidence for the diagnosis of generalized or site-specific bone loss providing straightforward clinical guidelines are followed.

Absorptiometry, Photon↗
PubMed1999

Regional differences in cortical porosity in the fractured femoral neck.

Although bone mass is a contributory risk factor for intracapsular hip fracture, its distribution and porosity within the femoral neck is also important for bone strength. In femoral neck biopsies from 13 women with intracapsular hip fracture (mean +/- SEM: 75.4+/-2.1 years, OP) and 19 cadaveric samples (9 men and 10 women [control], aged 79.4+/-1.7 years), a segmental analysis was used to quantify circumferential variations in the characteristics of cortical bone haversian systems. In female control femoral necks, there was an increasing porosity gradient between the inferior (I) (7.7+/-0.6%) and superior regions (S) (16.05+/-1.8%,p < 0.005). In walking, these regions undergo compression and tension, respectively. In men, a similar trend was observed, but the differences were not significant (I: 11.1+/-1.2%; S: 14.1+/-1.7%; p = 0.133). This porosity gradient was not maintained in the fracture group (I: 10+/-1%; S: 12.65+/-1.2%). In contrast, porosity in the fracture group was greatest in the anterior cortex, being 41% higher in that quadrant than in controls (p = 0.06). The areal density of haversian canals ranged from 16.7 to 21.3 canals/mm2 with no significant differences between fractures and controls. In the control women, mean canal diameter was highest in the superior region (60+/-2.8 microm), and these canals were significantly larger than those in the inferior region (49.4+/-1.4 microm, p < 0.05). This difference was less marked in the fracture cases (I: 53.21+/-2.5 microm; S: 59.1+/-2.8 microm; p = 0.0878). Although the mean canal diameter in the anterior quadrant of the fracture cases was higher than in the control women this did not reach significance (OP/F: 59.5+/-3 microm; control/F: 52.7+/-2.6 microm; p = 0.106). However, the proportion of "giant" canals with diameters >385 microm (defined as the top 0.5% in the controls) was doubled in the anterior region of the fracture cases (OP/F: 1.28%; control/F: 0.69%; p < 0.005). Porosity is related to the square of the canal radius; therefore, such canals make a substantial contribution to cortical porosity. Previous work has shown that the elastic modulus of bone decreases approximately as the square root of porosity. Therefore, the increased porosity and the higher prevalence of "giant" canals have a markedly negative influence on the ability of the cortical shell to withstand stresses associated with a fall. The mechanisms responsible for the localized generation of "giant" haversian canals, and ultimately the "trabecularization" of the cortex, require further investigation.

Adaptation, Physiological↗
PubMed1999

Determinants of the first decade of bone loss after menopause at spine, hip and radius.

This study documented bone loss at three different sites in the early postmenopausal period, and examined potential predictors. Forty-three women underwent repeated measurements of bone density at the lumbar spine, proximal femur and distal radius for up to 14 years. Individual rates of bone loss were calculated for the spine and hip; for radial trabecular bone, rates were calculated separately for two time periods, earlier and later after menopause. In the spine and radius, initially high rates of loss diminished with time after menopause. No positive correlations for bone loss were found between the three sites, suggesting that faster than average bone loss was specific to individual bones. High body mass index (BMI) was significantly protective against fast bone loss at the spine and radius; in the spine, each unit increase in BMI was associated with a approximately 5% reduction in the rate of bone loss. Of the other variables measured (maximum oxygen consumption, lean body mass, fat mass, mean psoas muscle area at the L3 level, hand grip strength as well as anthropometry) only bone densitometry was sufficiently predictive to help guidance on hormone replacement or other prophylactic therapy. The data suggest that the known relationship between excessive leanness and risk of osteoporosis and vertebral fracture after menopause might in part be due to fast post-menopausal bone loss. Because bulk of psoas muscle was associated with low spine loss rates, the data also support a role for applied muscular loading in local maintenance of bone density.

Adult↗
PubMed1999

Measurement imprecision in vertebral morphometry of spinal radiographs obtained in the European Prospective Osteoporosis Study: consequences for the identification of prevalent and incident deformities.

Several algorithms are currently in use for evaluating vertebral deformities from plain lateral radiographs of the lumbar and thoracic spine. However, the effects of measurement imprecision as well as uncertainties over image magnification on the correct identification of prevalent and incident vertebral deformities with these algorithms has been little studied. In a pilot study for the European Prospective Osteoporosis Study (EPOS), plain radiographs were submitted to a single central evaluating centre for measurement of vertebral height from T4 to L4. The thoracic and lumbar spines were imaged on separate films, and we have assessed the precision of measurement of vertebral heights and height ratios. The standard deviation of the differences between films of each of three height measurements ranged from 1.1 to 1.2 mm. A two-stage strategy for identifying incident deformities was devised. This required that the vertebra be a prevalent deformity at the time of the second radiograph and also that at least one of the vertebral ratios should have changed significantly since the first radiograph. The second stage removed all but two of the 18 vertebrae flagged positive in the first stage but not considered to be certain incident fractures by clinical reading of the radiographs.

Aged↗
PubMed1999

Structure of the femoral neck in hip fracture: cortical bone loss in the inferoanterior to superoposterior axis.

Although bone mass is a contributory risk factor for hip fracture, its distribution about the femoral neck is also important. Femoral neck biopsies were obtained from 13 females with intracapsular hip fracture (fracture: mean age 74.3 +/- 2.3 years [SEM]) and 19 cadaveric samples (control: 9 males and 10 females 79.4 +/- 1.7 years) and the areas of cortical and cancellous bone were quantitated in octants. In the control group, although males had larger bones than females, the proportions of cortical and cancellous bone were not different (p > 0.05) between the genders. The total amount of bone, as a proportion of bone + marrow, was significantly reduced in the fractures compared with the female controls (%Tt.Ar: fracture 27.83 +/- 1.18, female control 33.62 +/- 1.47; p = 0.0054). Reductions in cortical bone area occurred in all regions but particularly in the inferior, inferoanterior, and anterior octants (p < 0.05). There were no differences between cases and controls in the regional amount of cancellous bone (all regions, p > 0.178). Marked reductions in mean cortical bone width between the fracture and female control group occurred in the anterior, inferoanterior (31%), and superoposterior (25%) regions. Representing cortical widths as simple Fourier functions of the angle about the center of area (R2adj = 0.79) showed in the cases that there was preservation of the cortical bone in the inferior region, with the proportional loss of cortical bone being greatest in the inferoanterior and superoposterior regions. It is concluded that loss of cortical, rather than cancellous, bone predominates in cases of femoral neck fracture. This loss occurs primarily along the inferoanterior to superoposterior axis. As this axis bears the greatest strain during a fall, it is hypothesized that specific thinning of the cortex in these regions leads to an exaggerated propensity to fracture in those so affected, above that resulting from an equivalent general decrease in bone mass.

Aged↗