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Osteoclastic cortical erosion as a determinant of subperiosteal osteoblastic bone formation in the femoral neck's response to BMU imbalance. Effects of stance-related loading and hip fracture.
Femoral neck fractures have previously been shown to be associated with increased cortical and endocortical remodeling, reduced wall thickness of endocortical packets and cortical porosity. Femoral neck width is associated positively with history of lifetime physical activity; so we hypothesized that exposure to mechanical loading may influence the subperiosteal osteoblastic response to the weakening effect of intracortical bone resorption. In 21 femoral neck biopsies from female subjects (13 with hip fracture), there was a positive association between osteoblastic periosteal alkaline phosphatase expression shown in frozen sections and the percentage of cortical canals internal to the subperiosteal surface showing evidence of osteoclastic erosion (Goldner's stain; p =0.03). This was stronger in the plane of locomotor loading and particularly strong in the inferior (compression) cortex ( p =0.002). In 35 cases and 23 age/gender-matched postmortem controls, osteoid-bearing cortical canals (%) were significantly elevated in the fracture cases compared with the controls within the anterior region. There was also a significant correlation between cortical and endocortical %OS/BS (percentage osteoid surface to bone surface) (fracture, n =12; control, n =12) over the whole biopsy ( p =0.041). Generally, these associations of intracortical with endocortical remodeling were consistent with both envelopes being regulated by common processes. These results support the concept that the slow growth of femoral neck width by subperiosteal apposition of bone occurs directly or, otherwise, in response to the weakening of the cortex as it is "trabecularized" by imbalance of bone multicellular units (BMU). This process, in turn, depends on cortical thinning and enlargement of canals with the formation of giant, composite osteons, the whole being more marked in cases of future hip fracture.
Predictive value of BMD for hip and other fractures.
UNLABELLED: The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.
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.
Calcaneum broadband ultrasound attenuation relates to vegetarian and omnivorous diets differently in men and women: an observation from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study.
Vegetarian diets have been suggested to be beneficial for bone health due to increased consumption of plant foods, including soya, or reduced consumption of meat. However, meat may also be beneficial for bone health. The evidence relating diet to bone health is based largely on studies of women, often in those at high risk of osteoporosis. Few studies have investigated dietary inter-relationships in men as well as women from general populations. We examined broadband ultrasound attenuation (BUA) of the calcaneum, using a CUBA clinical instrument, in 6,369 men and 5,379 postmenopausal women. The population was divided into four groups according to vegetarian status and frequency of soya consumption, which was defined by response to a food frequency questionnaire that estimates frequency of consumption of food types over the year prior to completion. Regular soya consumers were defined as those who ate soya products with a frequency of between once a day and once a week. Calcaneum BUA in vegetarian men was significantly lower than omnivores by approximately 6% (5 dB/MHz) and was 15% (13.6 dB/MHz) lower in those who were also regular soya consumers. This difference remained after adjustment for age, height, weight, smoking habit, physical activity, selected foods and nutrients and exclusion of those with a prior history of osteoporosis, fractures or cancer. Calcaneum BUA in omnivorous men with regular soya consumption was not lower than the remaining population. In women, there were no significant differences by usual dietary pattern. This surprising finding indicates that regular soya intake is not associated with better bone indices in vegetarian men. The difference in BUA was not explained by the known common covariates; however, it is possible that other aspects of lifestyle associated with these eating behaviors might explain this observation. Plausible mechanisms exist for our findings; soya contains phytoestrogens, likened to naturally occurring estrogens, and meat has been shown to influence levels of IGF-1 and sex hormone binding globulin, which may be related to bone health. Our findings emphasize the need for further research and investigation into dietary inter-relationships and bone health and the effects of vegetarian status, including consumption of soya-based foods, in men as well as women.
Rapid long-term bone loss following stroke in a man with osteoporosis and atherosclerosis.
Bone loss in humans has been reported where there is reduced mechanical loading such as in space flight, spinal cord injury, and stroke. Whether osteoporotic patients are susceptible to further bone loss in states of underloading such as hemiparesis is unknown. Here we report the case of a 64-year-old man with established idiopathic osteoporosis and atherosclerosis who presented with a right middle cerebral artery territory stroke. Annual bone mineral density measurements were made at the left hip and spine before and after left hemiparesis. The left total hip T-score was -3.2 before the stroke. Following stroke, there was rapid and sustained bone loss with a reduction in bone mineral density (BMD) of 21.6% over 3 years despite oral bisphosphonate therapy. There was also an unexpected decline in vertebral BMD after the stroke. This is the first report of the accelerated effect of hemiplegia on bone loss in an already osteoporotic skeleton.
Osteocytic expression of constitutive NO synthase isoforms in the femoral neck cortex: a case-control study of intracapsular hip fracture.
UNLABELLED: NO is an osteocytic signaling molecule that can inhibit osteoclasts. The NO synthases eNOS and nNOS were expressed by >50% of osteonal osteocytes in controls. Hip fracture cases showed +NOS osteocytes only in deep osteonal bone, and 25-35% reduced expression overall. These data are consistent with increased osteonal vulnerability to deep osteoclastic attack. INTRODUCTION: Osteocytes may regulate the response to mechanical stimuli in bone through the production of local signaling molecules such as NO derived from the NO synthase eNOS. Because NO is inhibitory to osteoclastic resorption, it has been suggested that osteocytes expressing eNOS act as sentinels, confining resorption within single osteons. Recently, nNOS has been shown to be present in osteocytes of adult human bone. MATERIALS AND METHODS: Cross-sections of the femoral neck (eight female cases of intracapsular hip fracture and seven postmortem controls; age, 68-91 years) were analyzed by immunohistochemistry. The percentages of osteocytes expressing each of these two isoforms were calculated, and their distances to the nearest canal surface were measured. RESULTS: The percentage of +nNOS osteocytes was lower in the fracture cases than in the controls (cases: 43.12 +/- 1.49, controls: 56.68 +/- 1.45; p < 0.0001). Compared with nNOS, eNOS expression was further reduced (p = 0.009) in the cases but was not different in the controls (cases: 36.41 +/- 1.53, controls: 56.47 +/- 2.41; p < 0.0001). The minimum distance of +eNOS or +nNOS osteocytes to a canal surface was higher in the cases compared with controls (eNOS: controls; 44.4 +/- 2.2 microm, cases: 61.7 +/- 2.0 microm; p < 0.0001; nNOS: controls: 52.4 +/- 1.7 microm, cases: 60.2 +/- 2.1 microm; p = 0.0039). +eNOS osteocytes were closer to the canal surfaces than +nNOS osteocytes in the controls by 8.00 +/- 4.0 microm (p = 0.0012). CONCLUSION: The proportions of osteocytes expressing nNOS and eNOS were both reduced in the fracture cases, suggesting that the capacity to generate NO might be reduced. Furthermore, the reduction in NOS expression occurs in those osteocytes closest to the canal surface, suggesting that the ability of NO to minimize resorption depth might be impaired. Further studies are needed on the regulation of the expression and activity of these distinct NOS isoforms.
Femoral neck cortical bone in female and male hip fracture cases: Differential contrasts in cortical width and sub-periosteal porosity in 112 cases and controls.
OBJECTIVES: To quantitate differences between cases of hip fracture and controls in cortical width around the mid-femoral neck in men and women. METHODS: Over 5 years, 64 (14 male) participants over age 55 (mean 79) years, who had never taken bone-active drugs and suffered intra-capsular hip fracture treated by arthroplasty, donated their routinely discarded distal intra-capsular femoral neck bone for histomorphometry. After embedding, complete femoral neck cross sections from the cut surface near the narrowest part of the neck were stained with von Kossa and cortical width was measured radially every 5 degrees of arc. Control material (n = 48, 25 male) was available through consented post mortems prior to the year 2000. Cortical widths were averaged for circumferential octants, each representing 45 degrees of arc. Divergence of individual cortical widths from their means was also examined. RESULTS: Because sections were required to have a complete cortex, sampling was biased towards cases with sub-capital versus trans-cervical fractures. Compared to sex- and age matched controls, male cases showed larger relative differences in cortical widths than female cases. Unexpectedly, cortical widths in female but not male cases also showed marked over-representation of extremely narrow (<0.1 mm) cortical widths, located mainly posteriorly. The numbers of these very narrow cortical widths observed per subject retrospectively predicted female fracture status in logistic regression independently of mean cortical width values. Together with mean cortical width differences, the numbers of measured cortical widths <0.1 mm (out of 72 measured) raised the sensitivity of predicting fracture status in women from 48 to 80% at 80% specificity. In almost all cases, very narrow cortical widths were identified in regions enclosing a cortical pore roofed on its endosteal surface by thin structural bone defined a priori as trabecular. CONCLUSIONS: Cortical widths <0.1 mm probably reflect zones where endosteal cortex has been trabecularised through expansion of an un-refilled sub-endosteal canal close to the periosteum. Persistent cortical defects occurring near the periosteal surface, where mechanical loading exerts its greatest stresses, are likely to result in extremes of localized concentrations of stress during a fall, unknown in young normal fallers. Such defects have the potential to help explain the excess of hip fractures among elderly women. Prevention of sub-periosteal tunnelling by osteoclasts might explain in part the additional benefits, beyond an increase in bone density, of treatments that reduce excessive bone resorption or else stimulate new bone formation on previously resorbed surfaces.