- Research article
- Open Access
- Open Peer Review
Femoral geometry, bone mineral density, and the risk of hip fracture in premenopausal women: a case control study
BMC Musculoskeletal Disordersvolume 17, Article number: 42 (2016)
The purpose of this study was to determine the relationships among hip geometry, bone mineral density, and the risk of hip fracture in premenopausal women.
The participants in this case–control study were 16 premenopausal women with minimal-trauma hip fractures (fracture group) and 80 age-and BMI-adjusted controls. Subjects underwent dual-energy X-ray absorptiometry (DXA) to assess BMD at the proximal femur and to obtain DXA-derived hip geometry measurements.
The fracture group had a lower mean femoral neck and total hip BMD than the control group (0.721 ± 0.123 vs. 0.899 ± 0.115, p <0.001 for the femoral neck BMD and 0.724 ± 0.120 vs. 0.923 ± 0.116, p <0.001 for the total hip BMD). In addition, participants in the fracture group had a longer hip axis length (HAL; p = 0.007), narrower neck shaft angle (NSA; p = 0.008), smaller cross sectional area (CSA; p < 0.001) and higher cross sectional moment of inertia (CSMI; p = 0.004) than those in control group. After adjusting for BMD, the fracture group still had a significantly longer mean HAL (p = 0.020) and narrower NSA (p = 0.006) than the control group.
BMD is an important predictor of hip fracture in premenopausal women. Furthermore, HAL and NSA are BMD-independent predictors of hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered.
Premenopausal women with low bone mineral density (BMD) are increasingly being identified . Although low BMD is a major risk factor for fracture in postmenopausal women, the clinical significance of low BMD prior to menopause is not known. Low hip BMD has been shown to predict hip fracture in postmenopausal and perimenopausal women [2–5], however, the relationship between BMD and fracture in premenopausal women is unclear. Currently, a diagnosis of osteoporosis in premenopausal women is made based only on clinical signs, and not BMD .
Fractures are caused by forces that exceed bone strength, and can occur at any age. Bone strength is determined by bone geometry, microarchitecture, and material properties such as BMD. Hip fracture is one of the most serious and undesirable outcomes of low bone strength . Dual energy X-ray absorptiometry (DXA) scans can provide hip geometric characteristics as well as classical BMD measurements [8, 9].
Hip structural analysis (HSA) is used to extract cross-sectional geometry data from DXA images of the proximal femur to calculate bone strength [10, 11]. Previous reports have suggested that there are associations between hip geometry and hip fracture risk in postmenopausal women [12–15]. Moreover, hip axis length (HAL), the distance from the base of greater trochanter to the inner pelvic rim, has been shown to be strongly correlated with the risk of hip fracture [16–20]. Whether HSA could be useful for clinical assessment of bone fragility prior to menopause remains unclear. Because hip fracture, although serious, is very uncommon in premenopausal women, little is known about the relationship between hip geometry and minimally traumatic hip fracture risk in premenopausal women. Thus, the purpose of this study was to determine the relationship between hip geometry, BMD, and the risk of hip fracture in premenopausal women.
A total of 16 female patients with hip fracture (fracture group) were enrolled for participation in this study through retrospective review of medical records from May 2005 to April 2014 at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government Boramae Medical Center. Figure 1 illustrates process of the patient enrollment. Only patients with fractures due to minor trauma, such as falls from a standing position or while walking, were included. Thirteen patients had femoral neck fractures, two patients had intertrochanteric fractures, and one patient had distal femur fracture. The control group consisted of 80 age- and body mass index (BMI)-matched female subjects from the Healthcare System Gangnam Center. BMD and geometrical parameters were also obtained from 2005 to 2014 in the control group. Premenopausal controls have undergone BMD for health check-up, although the Korean Society of Bone and Mineral Research guidelines do not suggest BMD should be routinely screened in young women. Menopausal status was self-reported or, in cases in which this information was missing, we assumed that women younger than 45 years were premenopausal. Exclusion criteria included the presence of secondary causes of osteoporosis (such as hyperthyroidism, Cushing’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, chronic kidney disease), a history of malignant disease, or medications (such as steroids or anticonvulsants) known to alter calcium and bone metabolism. The study was approved by the ethics committees of Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government Boramae Medical Center.
Bone mineral density, hip geometry, and demographic data, including age, height, and body weight were collected. Measurements of BMD were made by DXA (Prodigy™, Lunar Corporation, Madison, WI, USA) at the proximal femur in all subjects capable of lying in a supine position with their hips extended and internally rotated 15°. In the fracture group, the mean time between the DXA scan and the fracture was 65 days (range, 0–533 days). Hip geometry measurements at the specific region of interest, including narrow neck, intertrochanteric, and femoral shaft measurements, were made using the standard DXA hip image with Encore software version 11.0, as previously described . The measured parameters were: HAL, the distance from the pelvic rim to the outer margin of the greater trochanter along the axis of the femoral neck; neck shaft angle (NSA), the angle between the derived axes of the femoral neck and shaft; cross sectional area (CSA), the amount of (cortical equivalent) bone surface area in the cross-section after excluding all trabecular and soft tissue spaces; cross sectional moment of inertia (CSMI), an index of structural rigidity that reflects distribution of mass about the center of a structural element; buckling ratio (BR), the relative thickness of the cortex as an estimate of cortical stability in buckling; and section modulus (SM), an indicator of the ability of the bone to resist maximum bending stress in the image plane.
All continuous data are presented as mean ± standard deviation. The significance of differences between the fracture and control groups was assessed using the Mann–Whitney U test. Analysis of covariance with correction for BMD was then performed. The relationships among bone geometric properties were evaluated using Pearson’s correlation coefficients. Univariate logistic regression analyses were used to evaluate the influence of BMD and geometry parameters on fracture risk. Statistical analyses were performed using SPSS version 22.0 software and differences were considered significant if p <0.05.
The baseline characteristics of the study populations are presented in Tables 1 and 2. Age, height, weight, and BMI did not significantly differ between groups. The mean age of the patients with hip fractures was 35.4 ± 6.0 years and their mean BMI was 19.2 ± 2.7 kg/m2. Compared with their age- and BMI-matched controls, the patients in the fracture group had a significantly lower mean femoral neck BMD (0.721 ± 0.123 vs. 0.899 ± 0.115, p < 0.001) and total hip BMD (0.724 ± 0.120 vs. 0.923 ± 0.116, p < 0.001), longer HAL (105.72 ± 4.88 vs. 101.80 ± 4.91, p = 0.007), narrower NSA (123.09 ± 2.81 vs. 126.07 ± 4.56, p = 0.008), smaller CSA (105.59 ± 15.85 vs. 130.92 ± 17.99, p < 0.001), and lower CSMI (7031.12 ± 1630.76 vs. 8521.96 ± 1652.57, p = 0.004). After adjusting for femoral neck BMD, the HAL and NSA were still significantly different between groups (p = 0.020 for HAL and p = 0.006 for NSA).
Relationships among hip geometric parameters and BMD
The results of Pearson’s correlation testing of the relationships among geometric parameters and between BMD and geometric parameters are presented in Table 3. Femoral neck BMD was positively correlated with total hip BMD, CSA, CSMI, and SM, and was negatively correlated with BR (p < 0.001 for all). There was a positive correlation between HAL and minimal neck width (p < 0.001), and CSA was also positively correlated with CSMI and SM (p < 0.001 for both). There were no meaningful correlations between NSA and any other parameters.
Hip geometric parameters, BMD, and the likelihood of hip fracture
Table 4 shows the contribution of BMD and bone geometry parameters to fracture risk. Univariate analysis of each variable was used to determine the odds ratio. Fracture risk increased 6.561-fold (p < 0.001) and 6.495-fold (p < 0.001) with decreases of 1 SD in femoral neck BMD and total hip BMD, respectively. Fracture risk also increased 4.038-fold (p < 0.001) and 3.431-fold (p = 0.001) with decreases of 1 SD in CSA and SM, respectively. Increases in HAL and NSA increased the risk of hip fracture (OR 2.212, p = 0.013 for HAL and OR = 2.377, p = 0.017 for NSA).
This case–control study of Korean premenopausal women showed that hip geometry is significantly associated with hip fracture, even prior to menopause. The relationship between hip BMD and hip fracture in premenopausal women is unclear. In this study, low hip BMD was still a major risk factor for hip fracture even in premenopausal women. When adjusted for BMD, HAL remained a significant predictor of hip fracture in premenopausal women. To the best of our knowledge, this is the first study to examine the association between HAL and risk of hip fracture in premenopausal women. When multiple logistic regression analysis was performed, only BMD was remained statistically significant (data not shown). However, when multiple logistic regression analysis using only geometric parameters was performed, long HAL and narrow NSA increased fracture risk with statistical significance (OR 0.247 and 4.484 with a 1 SD decrease in the variable, respectively; data not shown). These results showed that BMD is an important factor for fracture risk and geometric parameters, especially HAL and NSA, are additional risk factors to contribute increasing fracture risk.
It is unclear why the young patients in this study suffered fracture due to minor trauma. The patients with fractures showed significantly low bone mass compared to controls. We postulate that patients with fractures may achieve lower peak bone mass. However, why they have a lower peak bone mass is also unknown. As well, altered hip geometry parameters seem to increase susceptibility to hip fracture.
HAL was one of the first geometric measures proposed as a predictor of hip fracture risk in postmenopausal women, independent of BMD at the femoral neck . A previous study found that an increase in HAL equivalent to 1 SD resulted in a 1.9-fold increase in the risk of femoral neck fracture and a 1.6-fold increase in the risk of trochanteric fracture in elderly women , this result is similar to our findings. HAL has also been proposed as a possible explanation for the ethnic difference in hip fracture incidence . A recent study confirmed that HAL is a strong predictor of hip fracture in women older than 40 years when adjusted for BMD and FRAX score . The results of the current study suggest that HAL is also a BMD-independent risk factor for hip fracture in premenopausal women. However, although HAL appears to be a BMD-independent predictor of hip fracture in both postmenopausal and premenopausal women, it may not be associated with hip fracture in men. In contrast to postmenopausal women, there is little evidence that men with hip fractures have longer HALs than age-matched controls [14, 23]. The mechanism by which an increase in HAL increases hip fracture risk in women is unclear; the increased risk has been shown to persist after adjustment for height and weight . Moreover, men generally have a longer HAL than women. Collectively, these findings suggest that HAL is a body size-independent risk factor. It has been proposed that HAL is indicative of the ability of the femur or pelvis to absorb the impact of a fall . The greater trochanter of the femur may extend further beyond the pelvis in people with a longer HAL than in those with a shorter HAL, causing hips with a longer HAL to be predisposed to non-traumatic fracture. Thus, HAL may be of clinical value in initial fracture risk assessment for premenopausal women.
In this study, the NSA was decreased in the fracture group compared with the control group; however, the reason for this is unclear. In a case–control study, NSA was significantly greater in postmenopausal women with femoral neck fractures than in women with trochanteric fractures . However, in this study, 13 of 16 subjects had femoral neck fractures. Previous studies of postmenopausal women have yielded conflicting results regarding the relationship between NSA and hip fracture [16, 25–28]. A recent study suggested that acute NSAs are associated with development of atypical femur fractures . Varus hips seem to be susceptible to fracture due to increased lateral cortical loading, and we speculate that this may be a potential mechanism of hip fracture development in the premenopausal women in our study.
In this study, we assumed that women younger than 45 years were premenopausal. The mean age at natural menopause was 50.2 ± 3.7 years from the Korea National Health and Nutrition Examination Survey (KNHANES) . Furthermore, in data from KNHANES 2008–2010, BMD was significantly decreased in women with age over 45 years . In terms of bone mass, we considered that women with age below 45 years were safely premenopause.
This study had several limitations. The most of them result from its small sample size and retrospective design. As well, we selected only age-and BMI-matched controls, clinical information of subjects were insufficient and confounding factors were not strictly controlled. However, the fact that the incidence of hip fracture prior to menopause is extremely rare should be considered.
The results of this study suggest that BMD is an important risk factor for hip fracture in premenopausal women. Furthermore, long HALs and acute NSAs are BMD-independent risk factors for hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered.
bone mineral density
body mass index
cross sectional area
cross sectional moment of inertia
Dual energy X-ray absorptiometry
hip axis length
Hip structural analysis
neck shaft angle
Ferrari S, Bianchi ML, Eisman JA, Foldes AJ, Adami S, Wahl DA, et al. Osteoporosis in young adults: pathophysiology, diagnosis, and management. Osteoporos Int. 2012;23(12):2735–48. doi:10.1007/s00198-012-2030-x.
Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312(7041):1254–9.
Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. 2002;359(9321):1929–36. doi:10.1016/S0140-6736(02)08761-5.
Melton 3rd LJ, Atkinson EJ, O'Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res. 1993;8(10):1227–33. doi:10.1002/jbmr.5650081010.
Torgerson DJ, Campbell MK, Thomas RE, Reid DM. Prediction of perimenopausal fractures by bone mineral density and other risk factors. J Bone Miner Res. 1996;11(2):293–7. doi:10.1002/jbmr.5650110219.
ISCD. ISCD Official Positions - Adult published online. 2013. http://www.iscd.org/official-positions/2013-iscd-official-positions-adult. Accessed Jan 2014.
Lee YK, Yoon BH, Koo KH. Epidemiology of osteoporosis and osteoporotic fractures in South Korea. Endocrinol Metab (Seoul). 2013;28(2):90–3. doi:10.3803/EnM.2013.28.2.90.
Beck TJ, Ruff CB, Warden KE, Scott Jr WW, Rao GU. Predicting femoral neck strength from bone mineral data. A structural approach. Invest Radiol. 1990;25(1):6–18.
Bouxsein ML, Karasik D. Bone geometry and skeletal fragility. Curr Osteoporos Rep. 2006;4(2):49–56.
Beck TJ, Looker AC, Ruff CB, Sievanen H, Wahner HW. Structural trends in the aging femoral neck and proximal shaft: analysis of the Third National Health and Nutrition Examination Survey dual-energy X-ray absorptiometry data. J Bone Miner Res. 2000;15(12):2297–304. doi:10.1359/jbmr.2000.15.12.2297.
Beck T. Measuring the structural strength of bones with dual-energy X-ray absorptiometry: principles, technical limitations, and future possibilities. Osteoporos Int. 2003;14 Suppl 5:S81–8. doi:10.1007/s00198-003-1478-0.
Ahlborg HG, Nguyen ND, Nguyen TV, Center JR, Eisman JA. Contribution of hip strength indices to hip fracture risk in elderly men and women. J Bone Miner Res. 2005;20(10):1820–7. doi:10.1359/JBMR.050519.
El-Kaissi S, Pasco JA, Henry MJ, Panahi S, Nicholson JG, Nicholson GC, et al. Femoral neck geometry and hip fracture risk: the Geelong osteoporosis study. Osteoporos Int. 2005;16(10):1299–303. doi:10.1007/s00198-005-1988-z.
Faulkner KG, Wacker WK, Barden HS, Simonelli C, Burke PK, Ragi S, et al. Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int. 2006;17(4):593–9. doi:10.1007/s00198-005-0019-4.
Leslie WD, Pahlavan PS, Tsang JF, Lix LM. Manitoba Bone Density P. Prediction of hip and other osteoporotic fractures from hip geometry in a large clinical cohort. Osteoporos Int. 2009;20(10):1767–74. doi:10.1007/s00198-009-0874-5.
Faulkner KG, Cummings SR, Black D, Palermo L, Gluer CC, Genant HK. Simple measurement of femoral geometry predicts hip fracture: the study of osteoporotic fractures. J Bone Miner Res. 1993;8(10):1211–7. doi:10.1002/jbmr.5650081008.
Gnudi S, Ripamonti C, Gualtieri G, Malavolta N. Geometry of proximal femur in the prediction of hip fracture in osteoporotic women. Br J Radiol. 1999;72(860):729–33. doi:10.1259/bjr.72.860.10624337.
Peacock M, Turner CH, Liu G, Manatunga AK, Timmerman L, Johnston Jr CC. Better discrimination of hip fracture using bone density, geometry and architecture. Osteoporos Int. 1995;5(3):167–73.
Crabtree NJ, Kroger H, Martin A, Pols HA, Lorenc R, Nijs J, et al. Improving risk assessment: hip geometry, bone mineral distribution and bone strength in hip fracture cases and controls. The EPOS study. European Prospective Osteoporosis Study. Osteoporos Int. 2002;13(1):48–54.
Faulkner KG, McClung M, Cummings SR. Automated evaluation of hip axis length for predicting hip fracture. J Bone Miner Res. 1994;9(7):1065–70. doi:10.1002/jbmr.5650090714.
Cummings SR, Cauley JA, Palermo L, Ross PD, Wasnich RD, Black D, et al. Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. Study of Osteoporotic Fractures Research Group. Osteoporos Int. 1994;4(4):226–9.
Leslie WD, Lix LM, Morin SN, Johansson H, Oden A, McCloskey EV et al. Hip Axis Length is a FRAX and Bone Density Independent Risk Factor for Hip Fracture in Women. J Clin Endocrinol Metab. 2015:jc20144390. doi:10.1210/jc.2014-4390.
Center JR, Nguyen TV, Pocock NA, Noakes KA, Kelly PJ, Eisman JA, et al. Femoral neck axis length, height loss and risk of hip fracture in males and females. Osteoporos Int. 1998;8(1):75–81. doi:10.1007/s001980050051.
Brownbill RA, Ilich JZ. Hip geometry and its role in fracture: what do we know so far? Curr Osteoporos Rep. 2003;1(1):25–31.
Partanen J, Jamsa T, Jalovaara P. Influence of the upper femur and pelvic geometry on the risk and type of hip fractures. J Bone Miner Res. 2001;16(8):1540–6. doi:10.1359/jbmr.2001.16.8.1540.
Bergot C, Bousson V, Meunier A, Laval-Jeantet M, Laredo JD. Hip fracture risk and proximal femur geometry from DXA scans. Osteoporos Int. 2002;13(7):542–50. doi:10.1007/s001980200071.
Gnudi S, Sitta E, Pignotti E. Prediction of incident hip fracture by femoral neck bone mineral density and neck-shaft angle: a 5-year longitudinal study in post-menopausal females. Br J Radiol. 2012;85(1016):e467–73. doi:10.1259/bjr/57130600.
Alonso CG, Curiel MD, Carranza FH, Cano RP, Perez AD. Femoral bone mineral density, neck-shaft angle and mean femoral neck width as predictors of hip fracture in men and women. Multicenter Project for Research in Osteoporosis. Osteoporos Int. 2000;11(8):714–20.
Taormina DP, Marcano AI, Karia R, Egol KA, Tejwani NC. Symptomatic atypical femoral fractures are related to underlying hip geometry. Bone. 2014;63:1–6. doi:10.1016/j.bone.2014.02.006.
Park HA, Park JK, Park SA, Lee JS. Age, menopause, and cardiovascular risk factors among korean middle-aged women: the 2005 Korea National Health and Nutrition Examination Survey. J Womens Health. 2010;19(5):869–76. doi:10.1089/jwh.2009.1436.
Kim BJ, Lee SH, Koh JM, Kim GS. The association between higher serum ferritin level and lower bone mineral density is prominent in women >/=45 years of age (KNHANES 2008–2010). Osteoporos Int. 2013;24(10):2627–37. doi:10.1007/s00198-013-2363-0.
This work was not funded by any research or training grants.
The authors declare that they have no competing interests.
SWK supervised the study design and data analysis, revised the manuscript and acted as the corresponding author. DHL participated in study design/data analysis and drafted the manuscript, and acted as first author. KYJ and ARH participated in data collection. JHK, KMK, CSS, and SYK provided useful discussions. All authors read and approved the final manuscript.