Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 37 records · Page 2Linked to original sources

PubMed2004

Does hip strength analysis explain the lower incidence of hip fracture in the People's Republic of China?

To explore whether there are ethnic differences in calculated hip strength that might explain the low incidence of hip fracture in China, we used Lunar DPX 'beta' version of hip strength analysis (HAS) and hip axis length (HAL) programs to compare hip geometry, calculated strength and densitometric values from Chinese subjects in Shenyang to those of Caucasian subjects in Oslo and Leuven participating in the European Prospective Osteoporosis Study (EPOS). Subjects were 210 Chinese and 403 Caucasian men and women aged 53-77 years. Parameters investigated included bone mineral density (BMD), bone mineral content (BMC), bone area (BA), cross-sectional moment of inertia (CSMI) and section modulus (both indicating strength and rigidity of the femoral neck), HAL, neck length (NL), neck diameter, tensile stress (Tstress) and compressive stress (Cstress) (indicating the stress in the femoral neck at its weakest cross section arising from walking or a standard fall, respectively), safety factor (SF, indicating the resistance to fracture for forces generated during walking) and fall index (FI, indicating the resistance to fracture from force generated during a fall in the greater trochanter). The Chinese men and women were significantly shorter and lighter than their Caucasian counterparts (P<0.01) and had significantly lower BMD, BMC and BA of the femoral neck (P<0.01). After adjusting for BA, weight and height, there was no significant ethnic difference in either gender in BMC. CSMI and section modulus were significantly lower, and HAL, NL and neck diameter were significantly shorter in the Chinese men and women (P<0.01). These differences all remained after adjusting for weight and height. There were no significant differences in Tstress, Cstress, SF and FI between ethnic groups in either gender. Most of the parameters of calculated hip strength in the Chinese subjects were similar to or poorer than those in the Caucasian subjects. There was no evidence to indicate that Shenyang Chinese have superior BMD or BMC or better calculated hip strength. The short HAL and NL of the population, however, could be an independent factor contributing to the low incidence of hip fracture.

Aged↗

PubMed2004

A meta-analysis of previous fracture and subsequent fracture risk.

Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Adolescent↗

PubMed2004

A family history of fracture and fracture risk: a meta-analysis.

The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.

Age Factors↗

PubMed2004

Femoral neck fragility: genes or environment?

As with other diseases that show exponentially increasing rates, hip fracture probably requires multiple prior events to become manifest. It is common ground that there are genetic, environmental, lifestyle and perhaps dietary determinants of risk of osteoporotic fracture as well as interactions between them. The key to secondary prevention is the understanding of how these components can be integrated into an effective assessment of the major risks of hip fracture after a previous fracture has occurred. The key to primary prevention is to understand both the pathological and physiological basis of hip fragility. It is not unreasonable to suppose that in a western lifestyle our limited and stereotypic patterns of locomotion from middle age onwards may offer considerably less protection than, for example, the more physically demanding activity of subsistence farming.

Environment↗

PubMed2003

Health-related quality of life and radiographic vertebral fracture.

BACKGROUND: Vertebral fractures are associated with back pain and disability; however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). METHODS: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. RESULTS: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. CONCLUSIONS: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.

Aged↗

PubMed2003

Hip section modulus, a measure of bending resistance, is more strongly related to reported physical activity than BMD.

We hypothesized that measures of physical activity would have a closer relationship with section modulus (SM), an indicator of bending resistance, than with bone mineral density (BMD) because physical activity might expand the bony envelope, which tends to reduce BMD for a constant bone mineral content. Four hundred twenty-three men and 436 women (mean age 72 years, SD =3) were recruited from a prospective population-based cohort study to a study of hip bone loss. Hip BMD was measured on two occasions 2-5 years apart (mean 2.7, DXA-Hologic 1,000 W). Hip structural analysis (HSA) software was used to calculate SM and BMD from the DXA scans on three narrow regions: the narrow neck (NN), intertrochanter (IT) and shaft (S). A physical activity and lifestyle questionnaire was administered at baseline. Multivariate repeated measures analysis of variance was used to model the associations between personal attributes (weight, height, age), physical activity and lifestyle variables with SM, cross-sectional area (CSA), sub-periosteal diameter (PD) and BMD. Men and women were analysed together after tests for interactions with gender, which were found not to be significant. In all regions female gender was associated with having lower values of all outcomes, and body weight was positively associated with all outcomes, i.e., SM, CSA, PD and BMD ( P<0.0001). Sub-periosteal diameter was positively associated with reported lifetime physical activity (IT and S, P<0.0001). There was a significant decline of BMD with age at the NN and S regions ( P<0.026), and the PD increased with age (NN and S, P<0.019). Previous fracture history was associated with having lower values of BMD, SM and CSA (except for S; P<0.022). Both section modulus and CSA were positively associated with heavy physical activity after age 50 years in all regions ( P<0.019), whereas NN BMD was the only BMD associate of heavy physical activity after 50 ( P=0.036). Time spent per week on recreational activities classified as no impact activity was positively associated with BMD, CSA and SM (multivariate P<0.016). In conclusion, proximal femur diameter is associated positively with reported life-long physical activity. If this is mediated through a loading related effect on sub-periosteal expansion, BMD would be an unsatisfactory outcome measure in physical activity studies since it is inversely related to projected bone area. SM in contrast was associated with several measures of recent physical activity and relates more directly to the bending experienced by the proximal femur in response to a given load. These data are consistent with an effect of mechanical loading to regulate bone strength through an anabolic effect maximal in the subperiosteal cortex, where the highest loading-related strains are experienced.

Absorptiometry, Photon↗

PubMed2003

Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age.

We measured the impact of diet, anthropometry, physical activity and lifestyle variables on rates of hip bone mineral density (BMD) loss in 470 white men and 474 white women aged 67-79 years at recruitment dwelling in the community. The subjects were recruited from a prospective population-based diet and cancer study (EPIC-Norfolk) in Eastern England. Dietary intake was measured at baseline using 7-day food diaries and used to calculate intakes of some 31 nutrients and 22 food groups. Standardised questionnaires were used to collect data on anthropometry, physical activity and lifestyle variables. BMD loss (percent per annum; % p.a.) was measured using dual-energy X-ray absorptiometry performed on two occasions an average of 3 years apart (range 2-5 years). The mean rate of BMD change at the total hip region was -0.17% p.a. (SD 1.3% p.a.) in men and -0.41% p.a. (SD 1.2% p.a.) in women. In both men and women, weight gain protected against (and weight loss promoted) BMD loss ( P<0.0001). Markers of current physical activity were protective. In men, an increase of 1 l/s in FEV(1) was associated with an increase in BMD at an average rate of 0.25% p.a. ( P=0.013). In women, for every ten trips made per day climbing a flight of stairs, BMD increased at a rate of 0.22% p.a. ( P=0.005) and additionally a 10% increase in activities of daily living score was associated with BMD increasing at a rate of 0.12% p.a. ( P=0.011) in women. Nutritional variation appeared to have less impact on BMD loss. In men there was no evidence of an effect of any of the nutrients evaluated. However, in women, low intake of vitamin C was associated with faster rate of BMD loss. Women in the lowest tertile (7-57 mg/day) of vitamin C intake lost BMD at an average rate of -0.65% p.a., which was significantly faster compared to loss rates in the middle (58-98 mg/day) and upper (99-363 mg/day) tertiles of intake, which were -0.31% p.a. and -0.30% p.a., respectively ( P=0.016). There was no effect of fruits and vegetables, combined or separately, on rate of BMD loss. The results confirm that weight maintenance (or gain) and commonly practiced forms of physical activity appear to protect against BMD loss in this age group. Measures such as ensuring good general nutrition to guard against weight loss in the non-overweight elderly and maintenance of physical fitness could be valuable in protecting against BMD loss. The protective effect of vitamin C in women needs to be further investigated in other prospective cohort or intervention studies.

Aged↗

PubMed2003

Increased cancellous bone in the femoral neck of patients with coxarthrosis (hip osteoarthritis): a positive remodeling imbalance favoring bone formation.

Osteoporosis is caused by an imbalance between bone resorption and formation which results in an absolute reduction in bone mass. In a previous study we highlighted a condition, osteoarthritis of the hip (coxarthrosis, cOA), where an imbalance between resorption and formation provided beneficial effects in the form of an absolute increase in bone mass. We demonstrated that the femoral neck in patients with cOA had increased cancellous bone area, connectivity and trabecular thickness which might contribute to the protection against fracture associated with the condition. The aim of the present study was to analyze forming and resorbing surfaces in coxarthritic cancellous bone to assess whether increased formation or reduced resorption could be responsible for these structural changes. Whole cross-sectional femoral neck biopsies were obtained from 11 patients with cOA and histomorphometric parameters compared with 14 age- and sex-matched cadaveric controls. The ratio of osteoid surface to bone surface was 121% ( p<0.001) higher in the cases but there was no significant difference in resorptive surface. The percentage osteoid volume to bone volume (%OV/BV; +270%, p<0.001) and osteoid width (O.Wi; +127%, p<0.001) were also higher in the cases. This study suggests that the increased cancellous bone mass seen in cases of cOA is due to increased bone formation rather than decreased bone resorption. Investigation of the cellular and biochemical basis for these changes might provide new insights into the pathogenesis of osteoarthritis and highlight novel biological mechanisms regulating bone multicellular unit (BMU) balance that could be relevant to developing new interventions against hip and other osteoporotic fractures.

Aged↗

PubMed2003

Evidence for bone formation on the external "periosteal" surface of the femoral neck: a comparison of intracapsular hip fracture cases and controls.

Age-related expansion of the external surface of the femoral neck in order to offset generalized bone loss is potentially an important mechanism whereby hip strength and hence resistance to hip fracture is maintained. However, it has been widely assumed that bone formation is precluded from this external interface due to the presence of a synovial membrane associated with the hip joint. In this study we have demonstrated histologically that bone formation does indeed occur on the outer "periosteal" surface of the proximal femoral neck. It was therefore hypothesized that an impairment or reduction in periosteal bone formation might be seen in cases of femoral neck fracture compared with age-matched controls. Qualitative analysis of whole femoral neck samples from female subjects and age- and sex-matched post-mortem controls demonstrated that these groups expressed similar distributions of the bone formation marker, alkaline phosphatase (AP), at the periosteal surface [whole biopsy mean % periosteal AP-positive surface: control=16.0 (range=0.5-43.0), fracture=13.4 (range=1.0-34.6), p=0.44]. In conclusion, despite a wide intersubject variation, bone formation at the femoral neck periosteum is a feature of elderly women even if they have had a hip fracture.

Aged↗

PubMed2003

The ratio of osteocytic incorporation to bone matrix formation in femoral neck cancellous bone: an enhanced osteoblast work rate in the vicinity of hip osteoarthritis.

Recently it has been shown that an inactivating mutation in the TGFb-SMAD3 signaling pathway, which increases the conversion of osteoblasts to osteocytes, is accompanied by bone loss combined with increased osteocyte density. We hypothesized that increased matrix TGFb, known to occur in osteoarthritis, might cause the reverse of these effects in man. Because coxarthrosis (cOA) is associated with a reduced risk of femoral neck fracture, whole cross-section femoral neck biopsies were obtained from 11 patients with femoral neck fracture, 14 patients with cOA, and 22 age-and sex-matched controls. Lacunar density (Lc x mm2), osteocyte density (Ot x mm2), and cancellous wall width (Cn x W x Wi), were compared between cases of coxarthrosis, femoral neck fracture (FNF) and controls. In cOA, Lc.mm2 was reduced by 24% (P <0.001) while in FNF it was increased by 20% (P <0.001). Cn x W x Wi was increased in cOA by 22% (P <0.05) and in FNF was reduced by 27% (P <0.001). Lc x mm2 was inversely related to percentage cancellous bone area (adj. r2 = 0.373; P <0.01) and wall widths, r2 = 0.382, P <0.001. The reduction in osteocyte lacunar density coupled with increased wall width is consistent with a model of cOA effects on bone in which increased levels of matrix TGFb might prolong the effective lifespan or work rate of the osteoblast and delay its incorporation into the matrix as an osteocyte. One possible approach to strengthening bone in osteoporosis might be to enhance the effective lifespan of the osteoblast by modulating TGFb-related pathway activity in its local environment.

Aged↗

PubMed2003

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Age Distribution↗

PubMed2003

Increased femoral neck cancellous bone and connectivity in coxarthrosis (hip osteoarthritis).

Patients with coxarthrosis (cOA) have a reduced incidence of intracapsular femoral neck fracture, suggesting that cOA offers protection. The distribution of bone in the femoral neck was compared in cases of coxarthrosis and postmortem controls to assess the possibility that disease-associated changes might contribute to reduced fragility. Whole cross-section femoral neck biopsies were obtained from 17 patients with cOA and 22 age- and sex-matched cadaveric controls. Densitometry was performed using peripheral quantitated computed tomography (pQCT) and histomorphometry on 10-microm plastic-embedded sections. Cortical bone mass was not different between cases and controls (P > 0.23), but cancellous bone mass was increased by 75% in cOA (P = 0.014) and histomorphometric cancellous bone area by 71% (P < 0.0001). This was principally the result of an increase of apparent density (mass/vol) of cancellous bone (+45%, P = 0.001). Whereas cortical porosity was increased in the cases (P < 0.0001), trabecular width was also increased overall in the cases by 52% (P < 0.001), as was cancellous connectivity measured by strut analysis (P < 0.01). Where osteophytic bone was present (n = 9) there was a positive relationship between the amount of osteophyte and the percentage of cancellous area (P < 0.05). Since cancellous bone buttresses and stiffens the cortex so reducing the risk of buckling, the increased cancellous bone mass and connectivity seen in cases of cOA probably explain, at least in part, the ability of patients with cOA to resist intracapsular fracture of the femoral neck during a fall.

Aged↗

PubMed2003

Bone remodeling at the endocortical surface of the human femoral neck: a mechanism for regional cortical thinning in cases of hip fracture.

UNLABELLED: Endocortical remodeling and wall thickness (W.Th.) were measured in femoral neck bone from 12 female fracture cases (81.3 +/- 1.5 years) and 12 sex-matched controls (81.9 +/- 1.9 years). Regionally, osteoid and eroded surface were increased, whereas W.Th. was reduced. These processes likely contribute to cortical bone loss seen in hip fracture. INTRODUCTION: Because periosteal expression of alkaline phosphatase was similar between cases and controls, we hypothesized that the mechanism causing the marked femoral neck cortical thinning associated with hip fracture may be net endocortical bone loss. METHODS: Twelve female cases of femoral neck fracture (mean age = 81.3 +/- 1.5 years) and 12 age- and sex-matched postmortem controls (mean age = 81.9 +/- 1.9 years) were included in the study. Samples of their femoral neck bone were embedded in methyl methacrylate, sectioned at 10 microm, and stained with Solochrome cyanine R and Goldner's trichrome for the detection of osteoid (%OS/BS) and resorption surfaces (%ES/BS) respectively. In addition, wall thickness (W.Th.) and lamellar thickness (Lm.Th.) data were also collected from identifiable endocortical bone packets as a measure of formative potential. RESULTS AND CONCLUSIONS: %OS/BS was significantly elevated in the anterior (control = 3.4 +/- 0.7: fracture = 11.0 +/- 2.3; p = 0.0001), inferior (3.4 +/- 1.0: 9.9 +/- 3.0; p = 0.0009), and posterior quadrants (3.2 +/- 0.8: 9.1 +/- 2.3; p = 0.0021). Only for anterior region was increased %ES/BS demonstrated in the fracture group (2.8 +/- 0.6: 5.3 +/- 0.7; p = 0.055). W.Th. (mm) was reduced only in the inferior region of the fracture cases (control = 33.7 +/- 1.2: fracture = 30.6 +/- 0.9; p = 0.013), whereas Lm.Th. was also reduced inferiorly (control = 2.7 +/- 0.08: fracture = 2.5 +/- 0.08; p = 0.042). These data suggest that an endocortical remodeling imbalance involving reduced bone formation within inferior region coupled with elevated anterior resorption may make an important contribution to the cortical thinning observed in cases of femoral neck fracture.

Aged↗

PubMed2003

Determinants of the size of incident vertebral deformities in European men and women in the sixth to ninth decades of age: the European Prospective Osteoporosis Study (EPOS).

UNLABELLED: More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. INTRODUCTION: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. METHODS: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. RESULTS AND CONCLUSIONS: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

Aged↗

PubMed2002

Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Age Distribution↗

PubMed2002

Defining incident vertebral deformities in population studies: a comparison of morphometric criteria.

Various morphometric criteria have been used to define incident vertebral deformity. The aim of this analysis was to compare the relative validity of two established criteria and a novel method in which these criteria were combined. Men and women aged 50 years and over were recruited from population registers across Europe and had lateral spinal radiographs performed using a standard protocol. A subsample of individuals had bone mineral density (BMD) at the spine or femoral neck. Subjects were followed prospectively and a subsample had repeat spinal radiographs a median of 3.8 years after the baseline survey. All radiographs were evaluated morphometrically in the radiology coordinating center in Berlin. Anterior, middle and posterior height were recorded in all vertebrae from T4 to L4. On the basis of these morphometric measurements incident vertebral deformity was defined using one of three methods: (i) the change method - a change in any vertebral height of 20% or more between films, plus the additional requirement that a vertebral body have changed in absolute vertebral height by 4 mm or more; (ii) the point prevalence method, where a vertebra satisfies criteria for a prevalent deformity (McCloskey-Kanis) on the follow-up, though not the baseline film; (iii) a combination of the height reduction and the point prevalence criteria. Paired films were also evaluated qualitatively by an experienced radiologist for the presence of incident vertebral deformity. Logistic regression was used to compare the three morphometric methods using known risk factors for vertebral deformity including age, baseline vertebral deformity and BMD, and the qualitative evaluation. Computer simulation was used to determine the potential degree of bias and loss of statistical efficiency due to misclassification for each of the three methods, using the radiologist's assessment of incident deformity as the reference. Six thousand eight hundred subjects were included in this analysis. Of these 450 had sustained an incident vertebral deformity according to at least one of the three morphometric methods. The distribution of risk factors was similar in the subjects who satisfied only one morphometric criterion and those who satisfied neither. However, the subjects who satisfied both criteria had a very different distribution of risk factors: they were older, more likely to be female, more likely to have had a previous vertebral deformity and more likely to have an incident fracture in the opinion of an experienced radiologist. Using computer simulation, at low incidence levels, combining the criteria led to greater statistical efficiency and less bias in estimating associations with risk factors. Thus in this analysis the combination of the point prevalence and 20% change in height criterion for defining incident vertebral deformity showed a stronger relationship with clinical risk factors than either single criterion. Its application in population-based studies would increase the likelihood of detecting risk factors for incident vertebral deformity for a given sample size.

Age Factors↗

PubMed2002

Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study.

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX 'beta' versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)2) and age were considered alongside femoral neck BMD (FN-BMD, g/cm2) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong's test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more proactive approach to identifying women at high risk of hip fracture in the community.

Absorptiometry, Photon↗

PubMed2002

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

Aged↗