PubMed Health⌕ Search

Biomedical subjects

Jonathan Reeve

Publications and source records attributed to Jonathan Reeve.

30 records · Page 2Linked to original sources
PubMed2004

Bone mineralization density and femoral neck fragility.

The traditional view of osteoporotic fractures is that they result from a reduction in bone mass combined with alterations in the micro-architecture. Apart from the effects of bone remodeling, the material properties of the remaining bone are thought to be unaffected. To test this, we compared the degree of matrix mineralization in femoral neck biopsies taken from cases of intracapsular hip fracture with age- and sex-matched postmortem controls. Whole femoral neck biopsies from seven female hip fracture cases (72-90 years) and nine controls (68-94 years) were embedded in methylmethacrylate, and sections stained with Solochrome Cyanin R for analysis of osteoid. The blocks were then diamond micro-milled, carbon coated, and analyzed for the degree of matrix mineralization using halogenated dimethacrylate standards for quantitative backscattered electron (qBSE) imaging (20 kV, entire block face, sampling interval 5 microm). The BSE gray scale was adjusted such that 0 corresponds to an electron backscattering coefficient of 0.1159 (approximately 1.70 g/ml) and 255-0.1519 (approximately 2.18 g/ml). Remodeling and mineralization data were analyzed for both the whole biopsy face and on a regional (anterior; inferior, posterior, or superior) basis. Over the whole biopsy, the level of mineralization was lower in the cases than the postmortem controls (-2.8%, P < 0.05). In both cases and controls, cortical mineralization was higher in the inferior (compressive) region compared with superior (tensile) region (P < 0.05). Mineralization was lower in all regions of the cases (inferior: -3.3%; posterior: -3.1%; anterior: -2.7%; superior: -1.6%) compared to the controls. Mineralization density in cancellous bone was not regionally dependent but was lower in the fracture cases (-3.5%; P = 0.001). Although there were weak relationships between osteoid formation (%O.Ar/B.Ar) and the mean level of mineralization in both cortical (P = 0.068) and cancellous (P < 0.01) bone, adjustment for this did not markedly affect the case-control differences. In conclusion, this study has shown that in cases of intracapsular hip fracture, matrix mineralization is reduced in the femoral neck. Unexpectedly, in view of the likely role of mild to moderate vitamin D deficiency osteopathy in hip fracture, this decreased mineralization was independent of osteoid indices and therefore potentially independent of bone age. This raises the possibility that alterations in the bone matrix such as excessive glycation or changes in the composition of the collagen fibrils affect its mineralization in hip fracture cases.

Aged↗
PubMed2004

Increasing mineral density after menopause in individual lumbar vertebrae as a marker for incident degenerative disease: a pilot study for the effects of body composition and diet.

OBJECTIVE: To investigate the potential utility of dual x-ray absorptiometry (DXA) in incidence studies of lumbar spinal spondyloarthropathy. METHODS: Fifty-eight women recruited after menopause to a study of spinal bone loss were measured every 2 years for over a decade. Five developed scan image evidence of patchy calcification and 10 developed statistically significant (p < 0.05) nonparallelism of their bone loss (or gain) in L2, L3, and L4. The number of years since menopause at which these abnormal calcification trends (ACT) occurred was made the outcome in Cox proportional hazard modeling. At baseline, diet was assessed twice using 3-day weighed intakes. Nutrients estimated included carbohydrate, fat, protein, fiber, calcium and other minerals, and 6 vitamins. Measurements at baseline of fat mass and other anthropometric variables were made. RESULTS: The best single explanatory variable for developing ACT was whole body fat mass. Dietary fat was also predictive (p = 0.05) and adding dietary vitamin D (obtained substantially from oily fish) as a second predictor improved the diet model further (to p = 0.006 for model). These 2 dietary variables remained significantly predictive when fat mass was adjusted for (p = 0.0003 for model). CONCLUSION: Serial DXA measurements of the lumbar spine have the potential to provide a new, low radiation-dose approach to early identification of localized abnormal spinal calcification in epidemiology and trials. Alongside body fat, dietary fat intake and its components may warrant further investigation as risk factors for incident degenerative disease of the spine.

Absorptiometry, Photon↗
PubMed2003

Changes in bone mineral density in the hip and spine before, during, and after the menopause in elite runners.

This study was undertaken to determine the degree of interaction between hormonal and athletic effects on changes in bone mineral density (BMD, g/cm(2)) with time in women around the menopause. Thirty-five elite female runners aged over 40 participated in a longitudinal cohort study of hip and spine bone density changes and had two measurements a mean of 4.1 years apart. Eighteen remained estrogenized throughout the study (E+ to +), ten remained postmenopausal throughout (E- to -), while seven showed a change in status (E- to +) or (E+ to -). At study exit, both postmenopausal E+ and E- subjects had significantly higher than expected broadband ultrasound attenuation (BUA) and velocity of sound (VOS) values at the calcaneus. However, Z-score 95% confidence intervals for BMD of the hip and spine embraced zero except at the femoral trochanter in E+ women. The E+ to + group did not lose bone at any site. The E- to - group lost bone significantly, but only at the femoral neck and spine at rates close to 1% annually. Multiple analysis of variance repeated measures analysis showed a significant interaction in the effects of estrogen exposure with DXA measurement site, with the femoral trochanter being less affected by E- status than the spine and femoral neck. Body mass index (BMI: weight/height(2), kg/m(2)) had a significantly positive effect on total hip and femoral neck BMD independently of estrogen status. In conclusion, in this pilot study, postmenopausal elite runners not on hormone replacement therapy lost BMD from the femoral neck and spine at the expected rates but in the femoral trochanter bone loss appeared reduced and in the calcaneus BUA and VOS were maintained close to young normal values.

Absorptiometry, Photon↗
PubMed2003

Effects of gender, anthropometric variables, and aging on the evolution of hip strength in men and women aged over 65.

Although gender differences in fall rates may partly explain the higher prevalence of fractures in elderly women than men, male bones may also be intrinsically stronger or suffer less structural degradation with age than those of women. We used hip structural analysis (HSA) to study gender differences in hip geometry and bone mineral density (BMD) as they evolved over time in elderly white men and women with the aim of identifying candidate biological pathways leading to heightened risk of hip fracture. We recruited 443 women and 439 men aged 67-79 years from a diet and cancer prospective population-based cohort study to a study of hip bone loss. Hip BMD was measured on two occasions 2-5 years apart by dual-energy X-ray absorptiometry and HSA software used to derive BMD and structural parameters at the narrow neck (NN), the intertrochanter (IT), and the shaft (S) regions. Structural indices calculated in each region were cross-sectional area (CSA)-amount of bone surface area in the cross section after excluding soft tissue space; section modulus (Z)-an index of bending resistance, subperiosteal width, endocortical width, cortical thickness; and cortical buckling ratio (CBR)-a measure of cortical instability. Compared to men, women had lower values of BMD, CSA, Z, subperiosteal width, endocortical width, and cortical thickness in all regions, except S endocortical width, after adjusting for weight, height, and age (P < 0.0001). CBR was higher in women than in men (P < 0.0001) in all regions. Longitudinal analysis of rates of change revealed faster rates of BMD decline in women than in men at the Hologic total hip, Hologic femoral neck, and IT regions (P < 0.029). Women had faster rates of subperiosteal and endosteal expansion than men at the NN (P < 0.011) and IT (P < 0.049) and faster increase in Z at the NN (P = 0.029). At the IT region, cortical thinning was faster in women than in men (P = 0.037) and CBR increased at a faster rate in women (P = 0.011). In conclusion, Z is lower in women than in men and expansion of the proximal femur occurs in both sexes, being faster in women than in men. Z does not decline at the same rate as BMD, implying that part of the effect of aging on BMD is due to expansion of the bony envelope without loss of bone mineral content. Faster expansion in the female femoral neck may in turn lead to greater fragility if wider diameter and thinner cortices become locally unstable.

Age Distribution↗
PubMed2003

Characteristics of a prevalent vertebral deformity predict subsequent vertebral fracture: results from the European Prospective Osteoporosis Study (EPOS).

The presence of a prevalent vertebral deformity increases the risk of a future vertebral fracture. The aim of this study was to determine whether certain characteristics of the prevalent deformity, including its shape and location in the spine, influenced this effect. The 3100 men and 3500 women who took part in this analysis were recruited from population registers for participation in the European Prospective Osteoporosis Study (EPOS). Subjects had lateral thoracic and lumbar spine x-rays at baseline, and again after a mean interval of 3.8 years. Prevalent morphometric vertebral deformities on the baseline film were identified by the McCloskey-Kanis method. Incident fractures were defined as vertebrae that also satisfied the McCloskey-Kanis criterion for prevalent deformities on the follow-up film, and in addition had at least one height (anterior, mid, or posterior) which had reduced by at least 20% between films. Poisson regression was used to assess the association between various characteristics of the prevalent deformity and the risk of an incident vertebral fracture, with generalised estimating equations used to allow for the fact that each subject contributed several vertebrae to the analysis. The risk of an incident fracture increased with the number of prevalent deformities: relative risk (RR) for one prevalent deformity 3.2 (95% confidence interval (CI); 2.1, 4.8); 9.8 (95% CI;6.1, 15.8) for 2; and 23.3 (95% CI;15.3, 35.4) for 3 or more. Relative risks differed significantly according to the shape of the prevalent deformity, ranging from 5.9 (95% CI; 4.1, 8.6) if the anterior and mid heights were reduced to 1.6 (95% CI;0.8, 3.2) if the posterior and mid heights were reduced. Risks varied also according to the severity of the deformity. There were fivefold differences in relative risk of incident fracture depending on the location of the prevalent deformity within the spine. Compared to vertebrae in subjects with no deformities at baseline, the relative risk of an incident fracture within three vertebrae of a prevalent deformity was greater (7.7 (95% CI;5.6, 10.5)) than the risk in more distant vertebrae (4.0 (95% CI;2.6, 6.0)). In summary, the risk of a subsequent vertebral fracture in individuals with preexisting deformities is importantly influenced by the characteristics of these deformities.

Age Factors↗
PubMed2003

UK Food Standards Agency Optimal Nutrition Status Workshop: environmental factors that affect bone health throughout life.

The UK Food Standards Agency (FSA) convened a group of expert scientists to discuss and review UK FSA- and Department of Health-funded research on diet and bone health. This research focused on the lifestyle factors that are amenable to change and may significantly affect bone health and the risk of osteoporotic fracture. The potential benefits of fruits and vegetables, meat, Ca, vitamins D and K and phyto-oestrogens were presented and discussed. Other lifestyle factors were also discussed, particularly the effect of physical activity and possible gene-nutrient interactions affecting bone health.

Bone and Bones↗
PubMed2002

Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone.

Bone is removed or replaced in defined locations by targeting osteoclasts and osteoblasts in response to its local history of mechanical loading. There is increasing evidence that osteocytes modulate this targeting by their apoptosis, which is associated with locally increased bone resorption. To investigate the role of osteocytes in the control of loading-related modeling or remodeling, we studied the effects on osteocyte viability of short periods of mechanical loading applied to the ulnae of rats. Loading, which produced peak compressive strains of -0.003 or -0.004, was associated with a 78% reduction in the resorption surface at the midshaft. The same loading regimen resulted in a 40% relative reduction in osteocyte apoptosis at the same site 3 days after loading compared with the contralateral side (P = 0.01). The proportion of osteocytes that were apoptotic was inversely related to the estimated local strain (P < 0.02). In contrast, a single short period of loading resulting in strains of -0.008 engendered both tissue microdamage and subsequent bone remodeling and was associated with an eightfold increase in the proportion of apoptotic osteocytes (P = 0.02) at 7 days. This increase in osteocyte apoptosis was transient and preceded both intracortical remodeling and death of half of the osteocytes (P < 0.01). The data suggest that osteocytes might use their U-shaped survival response to strain as a mechanism to influence bone remodeling. We hypothesize that this relationship reflects a causal mechanism by which osteocyte apoptosis regulates bone's structural architecture.

Animals↗
PubMed2002

Falls, fractures, and osteoporosis after stroke: time to think about protection?

BACKGROUND: Osteoporosis is a significant complication of stroke. The clinical course of hemiplegic stroke predisposes patients to disturbed bone physiology. Sudden immobility and unilateral loss of function unload the skeleton at key areas such as the affected hip. This is manifest by an early reduction in bone density at this site. Stroke patients may also have motor, sensory, and visual/perceptual deficits that predispose them to falls. These factors result in an early but sustained increase in hip fractures after stroke. SUMMARY OF COMMENT: Potential bone loss is often overlooked in stroke treatment. Morbidity and mortality from hip fractures might be reduced by preventing bone loss at an early stage. In the crucial first year after stroke, bone loss seems to be due to accelerated resorption. Bisphosphonates are the drugs of choice in preventing osteoclastic bone resorption, but oral administration soon after stroke may be impractical. Potent new intravenous bisphosphonates have been used in postmenopausal women with osteoporosis with good preliminary results. Effective dosing regimens for osteoporosis have included a single annual or semiannual injection of bisphosphonate as well as weekly oral dosing. This article reviews the current literature on osteoporosis and hip fractures after stroke, making a case for a trial of intravenous bisphosphonates early after stroke. CONCLUSIONS: Hip fracture after stroke is an increasingly recognized problem. Measures to prevent bone loss and preserve bone architecture have not been part of stroke management thus far. Because rapid bone loss is a risk factor for fracture, we believe that a randomized, placebo-controlled trial of intravenous bisphosphonates given in the early phase of stroke rehabilitation is indicated.

Accidental Falls↗
PubMedDate not supplied

Relation between age, femoral neck cortical stability, and hip fracture risk.

BACKGROUND: Hip fracture risk rises 100 to 1000-fold over 60 years of ageing. Loss of resistance to bending is not a major feature of normal ageing of the femoral neck. Another cause of fragility is local buckling or elastic instability. Bones adapt to their local experience of mechanical loading. The suggestion that bipedalism allows thinning of the underloaded superolateral femoral neck cortex arises from the failure of walking to transmit much mechanical load to this region. We aimed to measure whether elastic instability increases greatly with age since it might trigger hip fracture in a sideways fall. METHODS: We measured with computed tomography the distribution of bone in the mid-femoral neck of 77 proximal femurs from people who died suddenly aged 20-95 years. We then calculated the critical stress, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall, as a threshold for elastic instability. FINDINGS: With normal ageing, this thin cortical zone in the upper femoral neck became substantially thinner. Relative to mean values at age 60 years, female cortical thickness declined by 6.4% (SD 1.1) per decade (p<0.0001), and critical stress by 13.2% (4.3) per decade (p=0.004) in the superoposterior octant compressed most in a sideways fall. Similar, but significantly smaller, effects were evident in men (p=0.004). This thinning compromised the capacity of the femur to absorb energy independently of osteoporosis. Patients with hip fracture had further reduced stability. INTERPRETATION: As women age, hip fragility increases because underloading of the superolateral cortex leads to atrophic thinning. Because walking does not sufficiently load the upper femoral neck, the fragile zones in healthy bones may need strengthening, for example with more well targeted exercise.

Absorptiometry, Photon↗