Fragility Hip Research Articles

Low osteocalcin/collagen type I bone gene expression ratio is associated with hip fragility fractures

IntroductionOsteocalcin (OC) is the most abundant non-collagenous bone protein and is determinant for bone mineralization.We aimed to compare OC bone expression and serum factors related to its carboxylation in hip fragility fracture and osteoarthritis patients. We also aimed to identify which of these factors were associated with worse mechanical behavior and with the hip fracture event. MethodsIn this case-control study, fragility fracture patients submitted to hip replacement surgery were evaluated and compared to a group of osteoarthritis patients submitted to the same procedure. Fasting blood samples were collected to assess apolipoproteinE (apoE) levels, total OC and undercarboxylated osteocalcin (ucOC), vitamin K, LDL cholesterol, triglycerides and bone turnover markers. The frequency of the apoε4 isoform was determined.Femoral epiphyses were collected and trabecular bone cylinders drilled in order to perform compression mechanical tests. Gene expression of bone matrix components was assessed by quantitative RT-PCR analysis. Results64 patients, 25 submitted to hip replacement surgery due to fragility fracture and 39 due to osteoarthritis, were evaluated. Bone OC/collagen expression (OC/COL1A1) ratio was significantly lower in hip fracture compared to osteoarthritis patients (p<0.017) adjusted for age, gender and body mass index. Moreover, OC/COL1A1 expression ratio was associated with the hip fracture event (OR ~0; p=0.003) independently of the group assigned, or the clinical characteristics. Apoε4 isoform was more frequent in the hip fracture group (p=0.029). ucOC levels were higher in the fracture group although not significantly (p=0.058). No differences were found regarding total OC (p=0.602), apoE (p=0.467) and Vitamin K (p=0.371).In hip fracture patients, multivariate analysis, adjusted for clinical characteristics, serum factors related to OC metabolism and gene expression of bone matrix proteins showed that low OC/COL1A1 expression ratio was significantly associated with worse trabecular strength (β=0.607; p=0.013) and stiffness (β=0.693; p=0.003). No association was found between ucOC and bone mechanics. Moreover, in osteoarthritis patients, the multivariate analysis revealed that serum total OC was negatively associated with strength (β=−0.411; p=0.030) and stiffness (β=−0.487; p=0.009). ConclusionWe demonstrated that low bone OC/COL1A1 expression ratio was an independent predictor of worse trabecular mechanical behavior and of the hip fracture event. These findings suggest that in hip fracture patients the imbalance of bone OC/COL1A1 expression ratio reflects disturbances in osteoblast activity leading to bone fragility.

Smoking is a predictor of worse trabecular mechanical performance in hip fragility fracture patients

Clinical risk factors (CRFs) are established predictors of fracture events. However, the influence of individual CRFs on trabecular mechanical fragility is still a subject of debate. In this study, we aimed to assess differences, adjusted for CRFs, between bone macrostructural parameters measured in ex-vivo specimens from hip fragility fracture patients and osteoarthritis patients, and to determine whether individual CRFs could predict trabecular bone mechanical behavior in hip fragility fractures. Additionally, we also looked for associations between the 10-year risk of major and hip fracture calculated by FRAX and trabecular bone mechanical performance. In this case-control study, a group of fragility fracture patients were compared with a group of osteoarthritis patients, both having undergone hip replacement surgery. A clinical protocol was applied in order to collect CRFs [body mass index (BMI), prior fragility fracture, parental history of hip fracture, long-term use of oral glucocorticoids, rheumatoid arthritis, current smoking, alcohol consumption, age and gender]. The 10-year probability of fracture was calculated. Serum bone turnover markers were determined and dual X-ray absorptiometry performed. Femoral head diameter was evaluated and trabecular bone cylinders were drilled for mechanical testing to determine bone strength, stiffness and toughness. We evaluated 40 hip fragility fracture and 52 osteoarthritis patients. Trabecular bone stiffness was significantly lower (p=0.042) in hip fragility fracture patients when compared to osteoarthritic individuals, adjusted for age, gender and BMI. No other macrostructural parameter was statistically different between the groups. In hip fragility fracture patients, smoking habits (β=-0.403; p=0.018) and female gender (β=-0.416; p=0.008) were independently associated with lower stiffness. In addition, smoking was also independently associated with worse trabecular strength (β=-0.323; p=0.045), and toughness (β=-0.403; p=0.018). In these patients, the 10-year risk of major (r=-0.550; p=0.012) and hip fracture (r=-0.513; p=0.021) calculated using only CRFs was strongly correlated with femoral neck bone mineral density but not with mechanical performance. Our data showed that among fragility fracture patients active smoking is a predictor of worse intrinsic trabecular mechanical performance, and female gender is also independently associated with lower stiffness. In this population, the 10-year risk of fracture using CRFs with different weights only reflects bone mass loss but not trabecular mechanical properties.

Better clinical results with postoperative antiosteoporotic therapy in hip fragility fractures

Better clinical results with postoperative antiosteoporotic therapy in hip fragility fractures

Incidence and costs of hip fractures vs strokes and acute myocardial infarction in Italy: comparative analysis based on national hospitalization records

ObjectivesAs osteoporotic fractures are becoming a major health care problem in countries characterized by an increasing number of older adults, in this study we aimed to compare the incidence and costs of hip fragility fractures in Italian elderly people versus those of major cardiovascular diseases (strokes and acute myocardial infarctions [AMI]) occurring in the whole adult population.MethodsWe analyzed hospitalization records maintained at the national level by the Italian Ministry of Health for the diagnosis of hip fractures (ICD-9-CM codes 820–821), AMI (code 410), hemorrhagic (codes 430, 431, 432) and ischemic strokes (codes 433–434), and TIA (code 435) between 2001–2005. Cost analyses were based on diagnosis-related groups.ResultsThe incidence of hip fractures in elderly people has increased (+12.9% between 2001 and 2005), as well as that of AMI (+20.2%) and strokes (hemorrhagic: +9.6%; ischemic: +14.7) occurring in the whole adult population; conversely, hospitalization due to TIA decreased by a rate of 13.6% between 2001 and 2005. In 2005, the hospital costs across the national health care system that were associated with hip fragility fractures in the elderly were comparable to those of strokes (both hemorrhagic and ischemic), which occurred in the whole Italian adult population. Moreover, these costs were higher than those generated by AMI and TIA. Rehabilitation costs following strokes reached about 3 billion Euros in 2005, but rehabilitative costs of hip fractures and AMI were comparable (about 530 million Euros in 2005).ConclusionThe burden of hip fragility fractures in Italy is comparable to that of AMI and strokes.

Differential characteristics of bone quality and bone turnover biochemical markers in patients with hip Fragility Fractures and Hip Osteoarthritis: results of a clinical pilot study

Bone density and quality alterations worsen the ability of osteoporotic bone to support prosthetic implants. The aim of our study was to evaluate potential differences in bone quality and bone turnover markers in aged individuals undergoing surgery for hip fragility fracture or hip osteoarthritis. Eighteen subjects with hip fragility fractures (Hip Fracture Group), 35 subjects with osteoarthritis of the hip (Hip Osteoarthritis Group) and 19 subjects with normal femoral bone mineral density (Control Group) were evaluated. Serum and urinary bone markers were assayed preoperatively in all surgical patients, and within 48 hours after fracture in the Hip Fracture, Osteoarthritis and Control groups. Histomorphometric analysis was performed on surgical samples. A significant alteration in calcium and PTH serum levels with hyperparathyroidism was observed in the Hip Fracture Group compared with Hip Osteoarthritis and Control Groups. C-Terminal telopeptides of type I-collagen (CTx) and tartrate resistant-acid phosphatase (TRAP), markers of bone resorption, were increased in the Hip Fracture Group compared with both Osteoarthritis and Control Groups (CTx: p<0.0007 and p<0.0039 respectively; TRAP: p<0.002 and p<0.0007). All subjects were vitamin D3-deficient, but no differences were found among the different groups. In addition, histomorphometric data showed better maintained connectivity in the Osteoarthritis Group compared with the Hip Fracture Group (p<0.0001). Our data show significant differences in bone turnover markers in patients undergoing hip prosthesis for fragility fractures, compared with patients operated for hip osteoarthritis.

Cost of fractures commonly associated with osteoporosis in a managed-care population

Objective: To examine direct costs of hip, vertebral, and non-hip non-vertebral (NHNV) fractures, and to estimate the rate of osteoporosis (OA) diagnosis and treatment in the fracture population.Methods: Subjects ≥ 45 years with a new hip, vertebral, or NHNV fragility (closed) fracture between June 30, 2002 and June 30, 2006 were studied retrospectively. All-cause and fracture-specific medical costs were calculated from medical claims in the 12-month baseline and follow-up periods. Total healthcare costs included pharmacy and medical costs. Diagnosis for OA and OA treatment were identified in both the baseline and follow-up period from diagnosis codes on medical claims for OA, and from pharmacy claims for treatment. Analyses were performed separately for commercial (COM) and Medicare Advantage (MA) populations and stratified by fracture type. Generalized linear models were estimated for total follow-up healthcare cost.Results: The study sample included 36,521 COM and 10,160 MA subjects. Hip fracture subjects had the highest follow-up medical costs in unadjusted and adjusted analyses (COM: mean $35,898; median $22,945; MA: mean $32,919; median $26,047). Follow-up costs were much higher than baseline costs. Fracture-related costs accounted for a large proportion of follow-up medical costs. Although rates of osteoporosis diagnosis and treatment increased from baseline to follow-up, the majority of both COM and MA subjects had no evidence of osteoporosis diagnosis or treatment in either period.Conclusions: Despite limitations of this study, including conventional generalizability issues, and sensitivity and specificity of claims-based diagnoses, results are consistent with other research and provide compelling results of substantial cost burden of fractures related to osteoporosis. Low rates of osteoporosis diagnosis and treatment among patients with costly fragility fractures underscore the opportunity for managed care organizations to initiate comprehensive disease management programs in osteoporosis.

Optimum frequency of exercise for bone health: Randomised controlled trial of a high-impact unilateral intervention

Introduction Exercise can increase bone strength, but to be effective in reducing fracture risk, exercise must be feasible enough to be adopted into daily life and influence potentially vulnerable skeletal sites such as the superolateral cortex of the femoral neck, where thinning is associated with increased fracture risk. Brief, high-impact exercise increases femoral neck bone density but the optimal frequency of such exercise and the location of bone accrual is unknown. This study thus examined (1) the effectiveness of different weekly frequencies of exercise on femoral neck BMD and (2) whether BMD change differed between hip sites using a high-impact, unilateral intervention. Methods Healthy premenopausal women were randomly assigned to exercise 0, 2, 4, or 7 days/week for 6 months. The exercise intervention incorporated 50 multidirectional hops on one randomly selected leg. BMD was measured by DXA at baseline and after 6 months of exercise. Changes in the exercise leg were compared between groups using ANCOVA, with change in the control leg and baseline BMD as covariates. RM-MANOVA was conducted to determine whether bone changes from exercise differed between hip sites. Results 61 women (age 33.6 ± 11.1 years) completed the intervention. Compliance amongst exercisers was 86.7 ± 10.6%. Peak ground reaction forces during exercise increased from 2.5 to 2.8 times body weight. The change in femoral neck BMD in the exercise limb (adjusted for change in the control limb and baseline BMD) differed between groups ( p = 0.015), being − 0.3% (− 1.2 to 0.6), 0.0% (− 1.0 to 1.0), 0.9% (− 0.1 to 2.0) and 1.8% (0.8 to 2.8) in those exercising 0, 2, 4 and 7 days per week, respectively. When BMD changes at upper neck, lower neck and trochanter were compared using RM-MANOVA, a significant exercise effect was observed ( p = 0.048), but this did not differ significantly between sites ( p = 0.439) despite greatest mean increases at the upper femoral neck. Conclusions Brief, daily hopping exercises increased femoral neck BMD in premenopausal women but less frequent exercise was not effective. Brief high-impact exercise may have a role in reducing hip fragility, but may need to be performed frequently for optimal response.

Targeted exercises against hip fragility

Compared to high-impact exercises, moderate-magnitude impacts from odd-loading directions have similar ability to thicken vulnerable cortical regions of the femoral neck. Since odd-impact exercises are mechanically less demanding to the body, this type of exercise can provide a reasonable basis for devising feasible, targeted bone training against hip fragility. Regional cortical thinning at the femoral neck is associated with hip fragility. Here, we investigated whether exercises involving high-magnitude impacts, moderate-magnitude impacts from odd directions, high-magnitude muscle forces, low-magnitude impacts at high repetition rate, or non-impact muscle forces at high repetition rate were associated with thicker femoral neck cortex. Using three-dimensional magnetic resonance imaging, we scanned the proximal femur of 91 female athletes, representing the above-mentioned five exercise-loadings, and 20 referents. Cortical thickness at the inferior, anterior, superior, and posterior regions of the femoral neck was evaluated. Between-group differences were analyzed with ANCOVA. For the inferior cortical thickness, only the high-impact group differed significantly (approximately 60%, p = 0.012) from the reference group, while for the anterior cortex, both the high-impact and odd-impact groups differed (approximately 20%, p = 0.042 and p = 0.044, respectively). Also, the posterior cortex was approximately 20% thicker (p = 0.014 and p = 0.006, respectively) in these two groups. Odd-impact exercise-loading was associated, similar to high-impact exercise-loading, with approximately 20% thicker cortex around the femoral neck. Since odd-impact exercises are mechanically less demanding to the body than high-impact exercises, it is argued that this type of bone training would offer a feasible basis for targeted exercise-based prevention of hip fragility.

Cortical and trabecular bone distribution in the femoral neck in osteoporosis and osteoarthritis

The increased hip fragility in osteoporosis has been attributed mainly to a thinning of the cortex. In contrast, hip arthritis (OA) is not associated with increased risk of hip fracture. The purpose of this study was to assess cortical and trabecular bone structures and their possible regional variability in the femoral neck taken from patients who sustained an osteoporotic hip fracture (OP) compared with patients with OA. We compared the distribution of bone in the ultradistal femoral neck in 21 postmenopausal women with OA (mean age: 66 ± 7.8 years) and 20 postmenopausal women with an osteoporotic hip fracture (OP) (mean age: 79.5 ± 1.9 years). Controlateral hip osteoporosis or osteopenia was confirmed in OP by DEXA ( T-score: − 2.5 ± 0.8 in OP; − 0.9 ± 1.3 in OA). Histomorphometric parameters of bone structure, architecture and connectivity were measured on sections from the ultradistal part of the femoral neck, divided in 4 quadrants. When compared to OA, cortical thickness was significantly decreased in OP ( p < 0.0005) but was the highest in the inferior part in both groups. Cortical porosity was higher in OA (13.48 ± 1.02 and 8.4 ± 1.07% in OA and OP respectively). Compared to OA, the trabecular bone volume was decreased by 50% in OP ( p < 0.0001) with a diminution of the trabecular number ( p < 0.01) and thickness ( p < 0.0001). In parallel, OP group was characterized by a poor connectivity evaluated by the decreased number of nodes ( p < 0.0001), higher trabecular bone pattern factor ( p < 0.0001) and greater marrow star volume ( p < 0.0001). The connectivity was the lowest in the inferior quadrant in OP but not in OA. Our data suggest that in addition to the cortical thinning, the loss of the trabecular bone mass and connectivity plays a role in the skeletal fragility associated with hip fracture. Furthermore, the spatial distribution of the trabeculae differs between OP and OA whereas cortical thinning is homogenous.

Sex-Specific Genetic Loci for Femoral Neck Bone Mass and Strength Identified in Inbred COP and DA Rats

Hip fracture is the most devastating osteoporotic fracture type with significant morbidity and mortality. Several studies in humans identified chromosomal regions linked to hip size and bone mass. Animal models, particularly the inbred rat, serve as complementary approaches for studying the genetic influence on hip fragility. The purpose of this study is to identify sex-independent and sex-specific quantitative trait loci (QTLs) for femoral neck density, structure, and strength in inbred Copenhagen 2331 (COP) and Dark Agouti (DA) rats. A total of 828 (405 males and 423 females) F(2) progeny derived from the inbred COP and DA strains of rats were phenotyped for femoral neck volumetric BMD (vBMD), cross-sectional area, polar moment of inertia (Ip), neck width, ultimate force, and energy to break. A whole genome screen was performed using 93 microsatellite markers with an average intermarker distance of 20 cM. Recombination-based marker maps were generated using MAPMAKER/EXP from the COP x DA F(2) data and compared with published Rat Genome Database (RGD) maps. These maps were used for genome-wide linkage analyses to detect sex-independent and sex-specific QTLs. Significant evidence of linkage (p < 0.01) for sex-independent QTLs were detected for (1) femoral neck vBMD on chromosomes (Chrs) 1, 6, 10, and 12, (2) femoral neck structure on Chrs 5, 7, 10, and 18, and (3) biomechanical properties on Chrs 1 and 4. Male-specific QTLs were discovered on Chrs 2, 9, and 18 for total vBMD, on Chr 17 for trabecular vBMD, on Chr 9 for total bone area, and on Chr 15 for ultimate force. A female-specific QTL was discovered on Chr 2 for ultimate force. The effect size of the individual QTL varied between 1% and 4%. We detected evidence that sex-independent and sex-specific QTLs contribute to hip fragility in the inbred rat. Several QTLs regions identified in this study are homologous to human chromosomal regions previously linked to QTLs contributing to femoral neck and related phenotypes.

A Novel DXA-Based Hip Failure Index Captures Hip Fragility Independent of BMD

Capability of a novel dual-energy X-ray absorptiometry (DXA)-based hip failure index (HiFI) to discriminate between hip fracture cases and controls was evaluated. Given the constraints of planar DXA, the femoral neck was assumed a foam-filled (∼trabecular bone), thin-walled (∼cortical bone) sandwich structure, while HiFI estimated the critical force sufficient to buckle the wall of such a structure. Proximal femur DXA data from 1379 women aged 65 yr and older, 268 with prior hip fracture were used. Comparison between standard areal bone mineral density (BMD), femur strength index (FSI), and HiFI was based on areas under receiver operatoring characteristic curves (AUC). The mean femoral neck BMD (SD) was 0.689 (0.109) g/cm 2 among the cases and 0.768 (0.119) g/cm 2 among the controls; the mean FSI 1.33 (0.36) and 1.54 (0.41), and the mean HiFI −0.28 (0.14) and −0.18 (0.15), respectively; all intergroup differences were highly significant ( p < 0.001). The intergroup difference for HiFI remained significant ( p < 0.002) after adjusting for age and BMD or FSI. The AUCs were 0.696 (95% confidence interval [CI]: 0.661–0.730) for BMD, 0.665 (0.630–0.700) for FSI, and 0.701 (0.666–0.736) for HiFI. In conclusion, HiFI may capture structural traits that account for femoral neck fragility independently of BMD or FSI. Obviously, the use of actual geometric and structural information from three-dimensional imaging of the femoral neck would help diminish the crude assumptions of the present DXA approach and reveal the true potential of the HiFI approach to gauge hip fragility and identify at-risk individuals for hip fractures.

Alterations in Proximal Femur Geometry in Children Treated with Glucocorticoids for Crohn Disease or Nephrotic Syndrome: Impact of the Underlying Disease

Proximal femur geometry was assessed in children and young adults treated with chronic GCs for CD or SSNS. Subperiosteal width and section modulus were significantly lower in CD and greater in SSNS compared with controls, highlighting the importance of the underlying disease, persistent inflammation, and alterations in lean mass. The impact of glucocorticoid (GC) therapy on bone structure during growth is unknown. Our objective was to characterize proximal femur geometry in children and young adults with Crohn disease (CD) or steroid-sensitive nephrotic syndrome (SSNS) compared with controls and to evaluate the influence of lean mass and GC therapy on bone parameters. DXA scans of the hip and whole body were obtained in 88 subjects with CD, 65 subjects with SSNS, and 128 controls (4-26 years of age). Hip structural analysis parameters (subperiosteal width, cross-sectional area [CSA], and section modulus in the narrow neck [NN], intertrochanteric region [IT], and femoral shaft [FS]), areal BMD, and whole body lean mass were expressed as Z scores compared with controls. Multivariable linear regression was used to adjust outcomes for group differences in age, sex, race, and height. Mean lean mass Z scores were lower in CD (-0.63, p < 0.001) and greater in SSNS (0.36, p = 0.03) compared with controls. Hip areal BMD Z scores were lower in CD (-0.73, p < 0.001) but not SSNS (-0.02, p > 0.2) compared with controls. In CD, Z scores for subperiosteal width (NN: -1.66, p < 0.001; FS: -0.86, p < 0.001) and section modulus (NN: -0.60, p = 0.003; FS: -0.36, p = 0.03) were significantly lower than controls. In contrast, in SSNS, Z scores were greater for IT subperiosteal width (0.39, p = 0.02), FS CSA (0.47, p = 0.005), and FS section modulus (0.49, p = 0.004). Alterations in section modulus in CD and SSNS were eliminated after adjustment for lean mass. Cumulative GC dose was inversely associated with FS subperiosteal width and section modulus only in CD. These data show that the effects of GC on proximal femur geometry during growth are influenced by the underlying disease, persistent inflammation, and alterations in lean mass. These data also provide insight into the structural basis of hip fragility in CD.

Magnetic resonance imaging of the femoral neck cortex

To determine the in vivo precision and accuracy of magnetic resonance imaging (MRI) in evaluating the thin (approximately mm) femoral neck cortex. Hip regions of 30 volunteers were scanned with standard 1.5 T MRI twice with repositioning, and the images of the narrow-neck cross-sections were obtained. Two radiologists independently delineated periosteal and endosteal cortical boundaries, and several structural variables were determined. For precision, 95% limits of agreement and coefficients of variation were calculated. Accuracy was determined with phantoms. In vivo precision of the directly delineated measurements varied from 0.9% (periosteal circumference) to 1.6% (total area), while the precision of the calculated variables remained poorer, from 7.3% (cortical to total area ratio) to 15.1% (torsional rigidity). The root-mean-square error of the cortical thickness measurement was 0.15 mm. Thin cortical bone at the narrowest location of the femoral neck can be delineated precisely and accurately with a standard clinical 1.5 T MRI device. MRI provides a feasible tool for the assessment of mechanically important cortical bone at the femoral neck and may be of clinical utility in assessing hip fragility.

Identification of a quantitative trait locus on rat chromosome 4 that is strongly linked to femoral neck structure and strength

Risk factors for osteoporotic hip fracture include reduced bone mineral density and poor structure of the femoral neck, both of which are heritable traits. Previously, we showed that despite similar body size, Fischer 344 (F344) rats have significantly different skeletal traits compared with Lewis (LEW) rats. To identify a gene or genes regulating fracture risk at the femoral neck, we mapped quantitative trait loci (QTL) for femoral neck density and structure phenotypes using a 595 F2 progeny derived from the inbred F344 and LEW strains of rats. Femoral neck phenotypes included volumetric bone mineral density (vBMD), neck width, femoral neck cross-sectional area and polar moment of inertia ( Ip). A 20-cM genome-wide scan was performed using 118 microsatellite markers and linkage analysis was conducted to identify chromosomal regions harbor QTL for femoral neck phenotypes. Strong evidence of linkage ( P < 0.01) to femoral neck vBMD was observed on chromosomes (Chrs) 1, 2, 4, 5, 7, 10 and 15. QTL affecting femoral neck structure and biomechanical properties were detected only on Chr 4 where the F344 alleles were shown to improve femoral neck structure, whereas these alleles had no effect on bone measurements at the lumbar spine and only modest effects at the femoral midshaft. In contrast, QTL on Chrs 1, 2 and 10 affected multiple skeletal sites. Several QTL regions in this study are homologous to human chromosomal regions, where linkage to femoral neck and related phenotypes has been reported previously. These findings represent an important first step in localizing and identifying genes that influence hip fragility.

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

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. 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. 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. 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.

Epidemiology of hip fractures in 2002 in Rabat, Morocco.

Hip fracture has never been studied before, either in Morocco or in the adjacent countries of the south bank of the Mediterranean Sea. The aim of this study was to investigate the incidence rate of hip fracture in 2002 in Rabat Province, a large area in the northwest of The Kingdom of Morocco, by the use of register information and medical records collected from the five public hospitals of the region. The hip fracture data were restricted to cervical or trochanteric types. There was a total of 150 hip fractures (83 in women and 67 in men) in the over-50-year-old population in the Province of Rabat during 2002. The age-adjusted 1-year cumulative incidence of hip fracture was 52.1/100,000 [95% confidence interval (CI) 40.9-63.3/100,000] in women and 43.7/100,000 (95% CI 33.3-52.2/100,000) in men. The standardized incidence rate against the 1985 US population was 80.7/100,000 (95% CI 78.5-93.0/100,000) for women and 58.5/100,000 (95% CI 47.9-68.1/100,000) for men. The mean (standard deviation) age of patients with a hip fracture was 70.7 (9.4) years for women and 70.4 (10.0) years for men. The overall female-to-male ratio of hip fracture was 1.19 for age-adjusted hip fracture incidence and 1.30 for standardized incidence. A marked increase in incidence rate was found for both men and women with increasing age, becoming exponential after the age of 50 years. The mean age for hip fracture was 70.7 (9.4) years in women and 70.4 (10.0) years in men (P > 0.05). Women had a cervical-to-trochanteric ratio of 0.97 compared to men, at 1.03. The characteristics of hip fractures described in this study suggest that fragility fractures occur in North Africa, although substantially less frequently than in most European, North American and Asian countries but more frequently than sub-Saharan African countries, in agreement with the north-south gradient observed in the epidemiology of osteoporosis. The low incidence of hip fragility fracture rate is most likely the result of reduced longevity in Morocco.

Two inbred rat strains that differ substantially in hip fragility.

One approach to identifying the genetic influences on skeletal phenotypes involves the creation and genetic mapping of a population of the second filial (F2) offspring derived from a cross of two inbred strains of rodents. The two inbred strains should be chosen based upon a large difference in the phenotype of interest, e.g., bone fragility. We found previously that considerable variation exists in fragility phenotypes among inbred strains of rats, and the phenotypic variation was site specific. In particular, two inbred rat strains, Copenhagen 2331 (COP) and Dark Agouti (DA), were found to differ significantly in femoral neck geometry and strength. The aim of this study was to further characterize hip fragility in COP and DA rats at 6 months of age using peripheral quantitative computed tomography (pQCT), microcomputed tomography (mCT), and biomechanical tests. COP rats had a significantly wider femoral head (P = 0.04) and neck (P = 0.007), significantly larger bone area and cortical bone area in femoral neck (P = 0.03 and P = 0.02, respectively), significantly greater total bone mineral content (BMC) and cortical BMC in femoral neck (P = 0.01 and P = 0.001, respectively), and 65% greater femoral neck cross-sectional moment of inertia (P = 0.02), as compared with DA rats. As a result, COP rats had 22% higher ultimate force (Fu), 68% higher ultimate displacement (du), and 81% higher work to failure (U) than DA rats in the femoral neck biomechanical test (P = 0.04, P = 0.01, and P = 0.02, respectively). The biomechanical properties for the femoral midshaft and lumbar vertebrae were virtually the same in the two rat strains, suggesting a hip-specific genetic effect on bone strength. These data indicate that significant phenotypic variation at the femoral neck site exists between these two inbred strains, and COP rats appear to have genes that specifically enhance the femoral neck structural properties and strength. Therefore these two inbred strains, COP with DA, may facilitate effective genetic studies of hip fragility.

Does exercise reduce the burden of fractures?

The null hypothesis that exercise has no effect on fracture rates in old age cannot be rejected on the basis of any published, randomized, prospective data. The view that exercise reduces the number of fractures is based on prospective and retrospective, observational cohort studies and case-control studies, all hypothesis-generating, not hypothesis-testing. Consistently replicated sampling bias may confirm the finding when evaluating other than randomized prospective studies. Better health, better muscle function, more muscle mass, better coordination may lead to exercise. The causal relationship could be between better health and exercise and better health and fewer fractures, not exercise and fewer fractures. The hypothesis should be tested in prospective, randomized studies evaluating hip, spine and other fragility fractures separately. Blinded studies assessing the effects of exercise can obviously not be done, but open trials can and should be undertaken to increase the level of evidence within the ...