Intertrochanteric Region Research Articles

Critical molecular regulators, histomorphometric indices and their correlations in the trabecular bone in primary hip osteoarthritis

This study examined differential gene expression, histomorphometric indices and relationships between these, in femoral trabecular bone from osteoarthritis (OA) patients and control (CTL) subjects, with the aim of identifying potential molecular drivers consistent with changes in structural and remodelling indices in the OA pathology. Bone samples from the intertrochanteric (IT) region were obtained from age and sex-matched cohorts of 23 primary hip OA patients and 21 CTL subjects. Real-time polymerase chain reaction (PCR) and histomorphometric analysis were performed on each sample and correlations between gene expression and histomorphometric variables determined. Alterations in gene expression, structural indices and correlations between these were found in OA bone compared to CTL. In OA bone, expression of critical regulators of osteoblast differentiation (TWIST1) and function (PTEN, TIMP4) were decreased, while genes associated with inflammation (SMAD3, CD14) were increased. Bone structural and formation indices (BV/TV, Tb.N, OS/BS) were increased, whereas resorption indices (ES/BS, ES/BV) were decreased. Importantly, significant correlations in CTL bone between CTNNB1 expression and formation indices (OS/BS, OS/BV, OV/BV) were absent in OA bone, indicating altered WNT/β-catenin signalling. TWIST1 expression and BV/TV were correlated in CTL bone, but not in OA bone, consistent with altered osteoblastogenesis in OA. Matrix metalloproteinase 25 (MMP25) expression and remodelling indices (ES/BS, ES/BV, ES/TV) were correlated only in OA pointing to aberrant bone remodelling in this pathology. These findings indicate an altered state of osteoblast differentiation and function in OA driven by several key molecular regulators. In association with this differential gene expression, an altered state of both trabecular bone remodelling and resulting microarchitecture were also observed, further characterising the pathogenesis of primary hip OA.

Dietary Equol and Bone Metabolism in Postmenopausal Japanese Women and Osteoporotic Mice

Equol binds to the estrogen receptor with greater affinity than its precursor, daidzein, an isoflavone found in soybeans. Inter-individual differences in the ability to produce equol may lead to differential effects of isoflavone intervention on human health. Here, we review previously published work from our laboratory on equol producer status and bone health in humans and in a mouse model of osteoporosis. We performed a 1-y, double-blind, randomized trial to compare the effects of isoflavone (75 mg of isoflavone conjugates/d; equivalent to 47 mg/d of the aglycone form) with those of placebo on bone mineral density (BMD), fat mass, and serum isoflavone concentrations in 54 early postmenopausal Japanese women classified by their equol-producer phenotype. Isoflavone intervention increased the serum equol concentration in equol producers but not in nonproducers (P < 0.04). The annualized changes in BMD in the total hip and intertrochanteric regions in the isoflavone-treated equol producers (−0.46 and −0.04%, respectively) were less than in the nonproducers (−2.28 and −2.61%, respectively). The annualized change in fat mass was lower in the equol producers compared with the nonproducers in the isoflavone group. The annualized changes in BMD and fat mass did not differ between the equol producers and nonproducers in the placebo group. Equol also inhibited bone loss and fat accumulation in estrogen-deficient osteoporotic mice. Our data suggest that prevention of bone loss and fat accumulation in early postmenopausal women by isoflavones may depend on an individual’s equol-producing capacity. J. Nutr. 140: 1373S–1376S, 2010.

Integrity of the osteocyte bone cell network in osteoporotic fracture: Implications for mechanical load adaptation

The human skeleton has the ability to modify its material composition and structure to accommodate loads through adaptive modelling and remodelling. The osteocyte cell network is now considered to be central to the regulation of skeletal homeostasis; however, very little is known of the integrity of the osteocyte cell network in osteoporotic fragility fracture. This study was designed to characterise osteocyte morphology, the extent of osteocyte cell apoptosis and expression of sclerostin protein (a negative regulator of bone formation) in trabecular bone from the intertrochanteric region of the proximal femur, for postmenopausal women with fragility hip fracture compared to age-matched women who had not sustained fragility fracture. Osteocyte morphology (osteocyte, empty lacunar, and total lacunar densities) and the degree of osteocyte apoptosis (percent caspase-3 positive osteocyte lacunae) were similar between the fracture patients and non-fracture women. The fragility hip fracture patients had a lower proportion of sclerostin-positive osteocyte lacunae in comparison to sclerostin-negative osteocyte lacunae, in contrast to similar percent sclerostin-positive/sclerostin-negative lacunae for non-fracture women. The unexpected finding of decreased sclerostin expression in trabecular bone osteocytes from fracture cases may be indicative of elevated bone turnover and under-mineralisation, characteristic of postmenopausal osteoporosis. Further, altered osteocytic expression of sclerostin may be involved in the mechano-responsiveness of bone. Optimal function of the osteocyte cell network is likely to be a critical determinant of bone strength, acting via mechanical load adaptation, and thus contributing to osteoporotic fracture risk.

Isolated fractures of the greater trochanter with occult intertrochanteric extension

Isolated fractures of the greater trochanter (GT) are relatively rare. The diagnosis can be done on routine radiographs, but it is difficult to fully define the geographic extent of these injuries. This study examined the pattern and extent of an injury shown by magnetic resonance imaging (MRI) and radionuclide bone scan (RBS) in patients whose plain radiographs revealed fractures limited to the GT. Between July 2004 and October 2008, 25 patients who displayed an isolated GT fracture on plain radiograph examination were examined by both MRI and RBS due to a suspicion of an extension into the intertrochanteric (ITC) region. The patients were then divided into two groups. Group A patients had an isolated fracture of GT, and group B patients had an occult fracture of ITC. All 25 cases were caused by a low-energy injury and plain radiographs showed non-displaced or minimally displaced isolated GT fractures. For 22 of the 25 patients, the result agreed with MRI and RBS. However, three patients had focal increased uptake at the GT region only according to RBS and an extension of signal intensity into the ITC region according to MRI. Group A and B comprised 5 and 20 patients, respectively. Of the group B patients, 8 had fractures with MRI evidence of complete extension across the ITC region and 12 had incomplete extension. Eleven of the 12 incomplete types showed an extension more than half way to the medial cortex. Fifteen group B patients underwent an internal fixation using a two-hole dynamic hip screw. Patients with an isolated fracture of GT can have a broader fracture extending into the ITC region than that diagnosed by standard radiographs. We recommend that all patients presenting with an isolated GT fracture on the plain radiographs should undergo MRI examination.

Diagnóstico por imagen del fibromixoma lipoesclerosante óseo

Liposclerosing myxofibrous tumor of bone is a benign lesion with a complex histologic structure. Its origin is uncertain, although it seems to be related to intraosseous lipomas and fibrous dysplasia, and it is sometimes impossible to distinguish from these two entities. It is usually located in the intertrochanteric region of the femur. Radiologically, it is a well-defined lytic lesion with sclerotic margins and high signal intensity in T2- weighted MR images. We present two cases with radiologic characteristics and location compatible with liposclerosing myxofibrous tumor of bone. In one case, PET studies suggested a malignant lesion. The diagnosis can be established on the basis of the radiological characteristics and location of the lesion: PET and histologic examination can sometimes lead to the wrong diagnosis.

Region-Specific Sex-Dependent Pattern of Age-Related Changes of Proximal Femoral Cancellous Bone and Its Implications on Differential Bone Fragility

Despite evident interest in age-related bone changes, data on regional differences within the proximal femur are scarce. To date, there has been no comprehensive study on site-specific age-related changes in the trabecular architecture of three biomechanically important femoral subregions (medial neck, lateral neck, and intertrochanteric region) for both genders. In this study we investigated age-related deterioration in the trabecular architecture of those three subregions of the femoral neck for both genders. The research sample included 52 proximal femora (26 males, 26 females; age range, 26-96 years) from Forensic Department at University of Belgrade. Bone sections from the three regions of interest were scanned by micro-CT at University of Hamburg. The study revealed that proximal femoral microarchitecture cannot be perceived as homogeneous and, more importantly, that the aging process is not uniform. Besides the initial intersite differences, microarchitecture changed differently with increasing age, maintaining significant differences between the regions. In addition, we observed a different aging pattern between genders: deterioration was most significant in the intertrochanteric region in women, while the lateral neck was most affected in men. This finding supports epidemiological data about the differential occurrence of cervical vs. trochanteric fractures in aging males and females. In conclusion, the aging process in the proximal femur cannot be regarded as a simple function of quantitative bone loss but, rather, as an alteration of specific architecture that may degrade bone strength.

Diagnosis and treatment of osteoporotic fractures

Diagnosis and treatment of osteoporotic fractures

Peripubertal estrogen levels and physical activity affect femur geometry in young adult women

The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. At age 17, subjects with the highest E2 levels in year 1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.

Women with hip fracture experience greater loss of geometric strength in the contralateral hip during the year following fracture than age-matched controls

This study examined femur geometry underlying previously observed decline in BMD of the contralateral hip in older women the year following hip fracture compared to non-fractured controls. Compared to controls, these women experienced a greater decline in indices of bone structural strength, potentially increasing the risk of a second fracture. This study examined the femur geometry underlying previously observed decline in BMD of the contralateral hip in the year following hip fracture compared to non-fractured controls. Geometry was derived from dual-energy X-ray absorptiometry scan images using hip structural analysis from women in the third cohort of the Baltimore Hip Studies and from women in the Study of Osteoporotic Fractures. Change in BMD, section modulus (SM), cross-sectional area (CSA), outer diameter, and buckling ratio (BR) at the narrow neck (NN), intertrochanteric (IT), and shaft (S) regions of the hip were compared. Wider bones and reduced CSA underlie the significantly lower BMD observed in women who fractured their hip resulting in more fragile bones expressed by a lower SM and higher BR. Compared to controls, these women experienced a significantly greater decline in CSA (-2.3% vs. -0.2%NN, -3.2% vs. -0.5%IT), SM (-2.1% vs. -0.2%NN, -3.9% vs. -0.6%IT), and BMD (-3.0% vs. -0.8%NN, -3.3% vs. -0.6%IT, -2.3% vs. -0.2%S) and a greater increase in BR (5.0% vs. 2.1%NN, 6.0% vs. 1.3%IT, 4.4% vs. 1.0%S) and shaft outer diameter (0.9% vs. 0.1%). The contralateral femur continued to weaken during the year following fracture, potentially increasing the risk of a second fracture.

Salvage of Failed Hip Fracture Fixation

Nonunion of fractures about the femoral neck and intertrochanteric hip regions is uncommon. Patients who develop nonunions of these fractures typically exhibit marked pain and disability, thereby presenting a treatment challenge to the orthopaedic surgeon. Factors that guide the choice of salvage treatment include the anatomic site of the nonunion, the quality of the remaining proximal bone and articular surface, and patient factors (such as age and activity level). In the younger patients with a well-preserved hip joint, treatment typically involves revision internal fixation with or without osteotomy or bone grafting. However, in older patients, it is more common to encounter poor remaining proximal bone stock or a badly damaged hip joint from hardware cutout. As such, conversion to hip arthroplasty is intended to help effectively restore function and relieve pain. With respect to salvage procedures for the femoral head, the major challenges in decision making include the choice of both internal fixation device and accurate preoperative planning. The challenges involved in planning to convert to hip arthroplasty include the need for acetabular resurfacing, selecting the femoral implant, and managing discontinuity of the greater trochanter. Furthermore, there are additional technical challenges that may be encountered, such as broken hardware, deformity, and femoral bone defects. Overall, salvage of nonunions of femoral neck and intertrochanteric hip fractures in properly selected patients can provide patients with good to excellent results.

Novel Approach of Predicting Fracture Load in the Human Proximal Femur Using Non-Invasive QCT Imaging Technique

This paper presents an analysis of predicting the load-bearing capacities of human femurs using quantitative computer tomography (QCT)-based beam theory. Cross-sectional images of 12 human cadaver femurs (intact bones, age: 39-77 years; male = 8, female = 4) were scanned in conjunction with a calcium hydroxyapatite phantom which has five chambers of known densities. The apparent densities obtained from the scans were used to evaluate the Young's modulus (E) by applying the established empirical relationships. The fracture load of a configuration that simulated single-legged stance was measured experimentally and compared with the predicted failure load using a composite beam theory, plane stress model of the femur. In this model, the failure was assumed to occur at the weakest cross-section through the bone determined from QCT-based structural analysis. In contrast to the other experimental investigations, the setup used in this study considers the entire length of a human femur and also incorporates a novel mechanical jig to mimic the realistic physiological scenario. In one of our earlier studies, simulated lytic defects of varying size were created at the inter-trochanteric region of femurs and their load-bearing capacities were calculated based on their structural properties. Both the results obtained from the current study as well as the ones from our previous study were used to assess the viability of the methodology. A high degree of correlation was observed when the predicted failure loads obtained from the intact femurs and previously studied defective femurs were compared with the ex vivo fracture loads. The coefficients of determination (R(2)) of QCT-derived predicted loads with respect to the measured failure loads were 0.80 for the intact femurs and 0.87 for the defective femurs. The results suggest that the QCT-derived beam analysis provides a viable approach for the assessment of load-bearing capacity in various clinical scenarios.

Analysis of bone matrix composition and trabecular microarchitecture of the femoral metaphysis in patients with osteonecrosis of the femoral head

Osteonecrosis of the femoral head (ONFH) usually affects young individuals. In advanced stages of ONFH, total hip replacement is the golden standard. However, survivorship after total hip replacement has been reported to be poorer in patients with ONFH compared to patients with primary osteoarthritis (OA). In radiological and histological studies, an impaired bone quality was found not only for the femoral head, but also for the intertrochanteric and metaphyseal region. We hypothesize that alterations of bone quality in the femoral metaphysis might contribute to early stem loosening. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling of the intertrochanteric regions and the proximal femoral canal in patients with ONFH and those with primary OA. The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by microCT analysis. Gene expression of BMP-2 is twofold higher in the proximal femur in the region of the greater trochanter of patients with ONFH compared to those with OA. The number of osteoblasts in the greater trochanter of patients with ONFH (253/mm(2)) is increased compared to patients with OA (156/mm(2)). Trabecular properties in ONFH bone are altered for bone volume (OA: 32 mm(3), ONFH: 51 mm(3)) and structure model index (OA: 2.2, ONFH: 1.6) in the proximal femoral canal, but not in the trochanteric regions. These alterations in bone metabolism and architecture might contribute to the higher rates of stem loosening after total hip replacement in patients with ONFH, however, further experimental and clinical studies are needed to support our findings.

Local Cancellous Bone Grafting for Osteonecrosis of the Femoral Head

This study reports a novel local bone graft technique for the treatment of osteonecrosis of femoral head (ONFH). From 1998 to 2005, a procedure using local bone grafting was performed for the treatment of ONFH in 11 patients. The local bone grafts were obtained from the intertrochanteric region and then impacted into the necrotic lesion. A wire coil was inserted into the remaining space after the grafting. At a mean follow-up of 61 months (range, 30 to 103 months), all 5 ARCO stage IIC hips survived but 3 of the 6 ARCO stage IIIA hips failed. The overall clinical success rate was 73%. This study demonstrates that local cancellous bone grafting combined with a space-filling device implanted into the ONFH is a promising procedure and the wire coil showed no interference to the remodeling of the femoral head after grafting.

Type of Hip Fracture in Patients With Parkinson Disease is Associated With Femoral Bone Mineral Density

Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. Type of hip fracture in patients with Parkinson disease is associated with femoral bone mineral density. Objective To investigate the association between bone mineral density (BMD) and hip fracture type (cervical or trochanteric) in a sample of fallers with Parkinson disease (PD). Design Observational study. Setting Rehabilitation hospital in Italy. Patients We investigated 1040 of 1120 white fallers consecutively admitted to a rehabilitation hospital for hip fracture. Thirty-eight (3.65%) of the 1040 patients suffered from PD secondarily. Thirty-eight controls matched for sex, age, and hip fracture type were found among the 1002 non-PD fallers. Interventions Not applicable. Main Outcome Measures BMD was assessed by dual-energy x-ray absorptiometry at a mean ± SD of 21.9±7.5 days after fracture occurrence in the 38 PD patients and 21.6±5.9 days after fracture occurrence in the 38 controls. Results BMD assessed at total femur, trochanter, and intertrochanteric region was significantly lower in the 15 PD patients with trochanteric fractures than in the 23 with cervical fractures; the mean T score differences were 0.57 (95% confidence interval [CI], 0.07–1.08; P=.028), 0.66 (95% CI, 0.04–1.28; P=.037), and 0.63 (95% CI, 0.11–1.15; P=.019), respectively. A significant association between femoral BMD and hip fracture type was found at logistic regression after adjustment for several confounders. Results in the 38 controls were similar to those obtained in the 38 PD fallers. Conclusions In a sample of PD fallers as in a control group of non-PD fallers, BMD levels assessed at 3 femoral sites were significantly lower in the patients who sustained trochanteric fractures than in those with cervical fractures of the hip.

Elevated intraosseous pressure in the intertrochanteric region is associated with poorer results in osteonecrosis of the femoral head treated by multiple drilling

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

Bone Metabolism in Adolescent Boys with Anorexia Nervosa

Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys. We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers. We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12-19 yr old. Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers. AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.

Initial stability of an implanted cement-canal prosthesis. Results in experimental studies on human cadaver femurs

Upon implantation of a cement-canal prosthesis in the proximal femur in total hip replacement, the bone cement is injected through the prosthesis via a system of drill holes. A second system of drill holes is used in this endoprosthesis to drain the distal femoral space as well as the cavities within the cement layer which form when the cement is being injected. Since the cement pressure is sustained until the cement has cured, substantial penetration of the cement into the cancellous bone can be achieved by using low intra-medullary cement pressures. Using cadaveric human femurs, the initial stability in the trabecular intertrochanteric region was determined in pull-out experiments for three different curing cement pressures (0.5 bar, 1.0 bar and 1.5 bar). The results were compared to corresponding controls in which a conventional cementation technique was used. With respect to the contact area of the bone/bone-cement interface, the initial stability increased by the factor 2.8 (cement-curing pressure 0.5 bar), 3.7 (cement-curing pressure 1.0 bar) and 2.9 (cement-curing pressure 1.5 bar) compared to the control group.

Micromechanical properties of human trabecular bone: A hierarchical investigation using nanoindentation

The ability to assess the risk of fracture, evaluate new therapies, predict implant success and assess the influence of bone remodeling disorders requires specific measurement of local bone micromechanical properties. Nanoindentation is an established tool for assessing the micromechanical properties of hard biological tissues. In this study, elastic modulus and hardness were quantified using nanoindentation for human trabecular bone from the intertrochanteric region of the proximal femur. These properties were demonstrated to be heterogeneous and highly correlated at the intraspicule, interspicule, and interspecimen levels. The results of this study have important implications for current understanding of structure-function relationships throughout the trabecular bone structural hierarchy.

Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women

Equol is more biologically active than its precursor daidzein, which is the principal isoflavone found in soybean. There are interindividual differences in the ability to produce equol; these may lead to differences in the effects of isoflavone intervention on human health. This study aimed to investigate whether the effects of soy isoflavones on bone and fat mass are related to an individual's equol status. We performed a 1-year double-blind, randomized trial to compare the effects of isoflavone (75 mg of isoflavone conjugates/day) with those of placebo on bone mineral density, fat mass, and serum isoflavone concentrations in early postmenopausal Japanese women who were classified based on their equol-producer phenotype. After 1 year, the isoflavone intervention significantly increased the serum equol concentration in the equol producers but not in the nonproducers. In the isoflavone group, the annualized changes in the bone mineral density of the total hip and intertrochanteric regions were -0.46% and -0.04%, respectively, in the equol producers and -2.28% and -2.61%, respectively, in the nonproducers; these values were significantly different (P<0.05 for both the regions). Significant differences were observed between the equol producers and nonproducers in the isoflavone group with regard to the annualized changes in the fat mass. No significant difference in the annualized changes in bone mineral density and fat mass was observed between the equol producers and nonproducers in the placebo group. Our data suggest that the preventive effects of isoflavones on bone loss and fat accumulation in early postmenopausal women depend on an individual's equol-producing capacity.

Bivariate Linkage Study of Proximal Hip Geometry and Body Size Indices: The Framingham Study

Femoral geometry and body size are both characterized by substantial heritability. The purpose of this study was to discern whether hip geometry and body size (height and body mass index, BMI) share quantitative trait loci (QTL). Dual-energy X-ray absorptiometric scans of the proximal femur from 1,473 members in 323 pedigrees (ages 31-96 years) from the Framingham Osteoporosis Study were studied. We measured femoral neck length, neck-shaft angle, subperiosteal width (outer diameter), cross-sectional bone area, and section modulus, at the narrowest section of the femoral neck (NN), intertrochanteric (IT), and femoral shaft (S) regions. In variance component analyses, genetic correlations (rho ( G )) between hip geometry traits and height ranged 0.30-0.59 and between hip geometry and BMI ranged 0.11-0.47. In a genomewide linkage scan with 636 markers, we obtained nominally suggestive linkages (bivariate LOD scores > or =1.9) for geometric traits and either height or BMI at several chromosomes (4, 6, 9, 15, and 21). Two loci, on chr. 2 (80 cM, BMI/shaft section modulus) and chr. X (height/shaft outer diameter), yielded bivariate LOD scores > or =3.0; although these loci were linked in univariate analyses with a geometric trait, neither was linked with either height or BMI. In conclusion, substantial genetic correlations were found between the femoral geometric traits, height and BMI. Linkage signals from bivariate linkage analyses of bone geometric indices and body size were similar to those obtained in univariate linkage analyses of femoral geometric traits, suggesting that most of the detected QTL primarily influence geometry of the hip.