Hip Geometry Parameters Research Articles

Differential effects of teriparatide, denosumab and zoledronate on hip structural and mechanical parameters in osteoporosis; a real-life study.

The aim of this study was to evaluate changes in hip geometry parameters following treatment with teriparatide (TPD), denosumab (Dmab) and zoledronate (ZOL) in real-life setting. We studied 249 patients with osteoporosis (OP) with mean [SD] age of 71.5 [11.1] years divided into 3 treatment groups; Group A received TPD; n = 55, Group B (Dmab); n = 116 and Group C (ZOL); n = 78 attending a routine metabolic bone clinic. Bone mineral density (BMD) was measured by DXA at the lumbar spine (LS), total hip (TH) and femoral neck (FN) prior to treatment and after 2years (Group A), after a mean treatment duration of 3.3 [1.3] years (Group B) and after 1, 2 and 3 doses of ZOL (Group C) to assess treatment response. Hip structural analysis (HSA) was carried out retrospectively from DXA-acquired femur images at the narrow neck (NN), the intertrochanter (IT) and femoral shaft (FS). Changes in parameters of hip geometry and mechanical strength were seen in the following treatment. Percentage change in cross-sectional area (CSA): 3.56[1.6] % p = 0.01 and cross-sectional moment of inertia (CSMI): 4.1[1.8] % p = 0.029 increased at the NN only in Group A. Improvement in HSA parameters at the IT were seen in group B: CSA: 3.3[0.67]% p < 0.001, cortical thickness (Co Th): 2.8[0.78]% p = 0.001, CSMI: 5.9[1.3]% p < 0.001, section modulus (Z):6.2[1.1]% p < 0.001 and buckling ratio (BR): -3.0[0.86]% p = 0.001 with small changes at the FS: CSA: 1.2[0.4]% p = 0.005, Z:1.6 [0.76]%, p = 0.04. Changes at the IT were also seen in Group C (after 2 doses): CSA: 2.5[0.77]% p = 0.017, Co Th: 2.4[0.84]% p = 0.012, CSMI: 3.9[1.3]% p = 0.017, Z:5.2[1.16]% p < 0.001 and BR: -3.1[0.88]% p = 0.001 and at the NN (following 3 doses): outer diameter (OD): 4.0[1.4]% p = 0.0005, endocortical diameter(ED): 4.3[1.67% p = 0.009, CSA:5.2[1.8]% p = 0.003, CSMI: 9.3[3.8]% p = 0.019. Analysis of the effect of OP therapies on hip geometry is useful in understanding the mechanisms of their anti-fracture effect and may provide additional information on their efficacy.

Association of Hip Geometry with Proximal Femoral Fracture in Elderly Population

Introduction: Hip fractures are a significant global health concern, particularly among the elderly population, with increasing incidence rates predicted in the coming decades. Although different factors like age-related osteoporosis, alcoholism, smoking, high BMI are established causes of hip fracture but none can fully explain the cause of hip fracture. Proximal hip geometry (HAL. FNAL, FNA, FHD, FND) may be associated with hip fracture and is under investigation with conflicting reports. Method: Our study is X-ray based prospective case-control study aiming to evaluate the association of hip geometry parameters with proximal femoral fractures in elderly population. We conducted study involving 102 subjects, including 34 cases with proximal femoral fractures and 68 controls. Various hip geometry parameters were calculated, tabulated and compared to see the difference in hip parameters among fractured and non-fractured group. Additionally, we calculated the mean and standard deviation among male and female subjects and compared between them Result: Our study revealed differences in HAL and FNAL between the case and control groups, suggesting their potential role as risk factors for proximal femoral fractures. However, no significant differences were observed in NSA, FHD, and FND between the two groups. Gender-wise analysis showed significant differences in HAL, FNAL, FHD, and FND between males and females, possibly due to variations in height among them. Conclusion: This study contributes to the understanding of hip fracture risk factors in the elderly population and underscores the importance of considering hip geometry parameters in fracture risk assessment. Larger studies are recommended to further validate these findings.

The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial

SummaryThis study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry.PurposeSome clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment.MethodsWe conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed.ResultsChanges in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03).ConclusionThe addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed.Trial registrationThe study was registered at Clinicaltrial.gov:NCT01232647.

Relationship of lower limb geometrics with femorotibial osteoarthritis in the toei cohort

Osteoarthritis (OA) is a common disease of joints that is more common in females than in males. It is characterized by severe knee degeneration, damaged cartilage and appearance of osteophytes. Hip geometry and morphometric parameters in the knee joint vary between the sexes and depend on the severity of OA and the presence of osteophytes. Very few studies have assessed this phenomenon; therefore in this study, we assessed the difference in hip geometry and morphometric parameters in the lower limbs of males and females and evaluated the association of the differences with the presence or absence of osteophytes. Three hundred and six knees volunteers (104 male knees and 202 female knees) from the Toei region were included in the study between 2012 and 2018. The parameters measured were from the anteroposterior and lateral views of the hip and anteroposterior view of the knee. The participants were divided into 4 groups based on the assessment for osteophytes: Group 1 had no osteophytes, Group 2 had lateral compartment osteophytes, Group 3 had medial compartment osteophytes, and Group 4 had osteophytes in both compartments. Males had an increased femoral neck-shaft angle, femoral-tibial angle, and plateau angle, and a decreased femoral offset, femoral neck length, fibular-tibial angle, and knee rotation index than females. Group 2 had a greater height of the hip center, the angle between the femoral mechanical axis and the femoral shaft axis, condylar-hip angle, and plateau angle than Group 1. Group 3 showed an increased abductor angle, the angle between the femoral mechanical axis and the femoral shaft axis. Group 4 showed an increased angle between the femoral mechanical axis and the femoral shaft axis, femoral-tibial angle, and a decreased patellar shift index and knee rotation index. The angle between the femoral mechanical axis and the femoral shaft axis, condylar-hip angle, femoral-tibial angle, plateau angle, patellar shift index, and knee rotation index were different in both sexes and may be dependent on the presence or absence of osteophytes.

Short Term Radiological Outcome of Combined Femoral and Ilium Osteotomy in Pelvic Reconstruction of the Child.

Background and Objectives: Reconstruction of the pelvic joint is a common way to address developmental dysplasia of the hip (DDH), as well as neurogenic dislocation of the hip (NDH) and Legg–Calvé–Perthes disease (LCPD) in children. The purpose of this study was to analyze the short-term radiologic outcome after hip reconstructive surgery either treated with sole osteotomy of the femur or in combination with iliac osteotomy in patients with DDH, NDH and LCPD. Materials and Methods: X-rays of 73 children, aged 2–18 years, with DDH, NDH and LCPD after hip reconstructive surgery were measured retrospectively and compared to the preoperative x-rays concerning various parameters to define hip geometry. The surgical procedures were femoral osteotomy (74), Salter innominate osteotomy (27), Pemberton osteotomy (27), open reduction (37), Chiari osteotomy (4). The pre-/postoperative acetabular index (AI), center-edge angle (CE) and Reimers migration index (RMI) were evaluated before and 3 months after surgery. Results: Hip geometry parameters improved significantly (RMI: preop/postop: 62.23% ± 31.63%/6.30% ± 11.51%, p < 0.001; CE: 11.53° ± 20.16°/30.58 ± 8.81°, p < 0.001; AI: 28.67° ± 9.2°/19.17 ± 7.65°, p < 0.001). Sub-group analysis showed a superior RMI in DDH compared with NDH 3 months after surgery (DDH/NDH: 2.77% ± 6.9%/12.94% ± 13.5%; p = 0.011). Osteotomy of the iliac bone (Salter innominate, Pemberton, Chiari) resulted in a significant improvement of the postoperative RMI compared to cases without osteotomy of the ilium (7.02 ± 11.1% vs. 16.85 ± 4.71%; p = 0.035). Conclusions: Femoral and pelvic osteotomies are effective to improve the radiological pelvic parameters in infants and adolescents with DDH, NDH and LCPD. In addition, the study found that the combination of femoral and pelvic osteotomy led to a better RMI than femoral osteotomy alone. Using the combined ilium and femoral osteotomy, it was possible to show the highest effect on correction of the hip geometry with respect to residual RMI.

Progressive lateralization and constant hip geometry in children with DDH, NDH, and LCPD following hip reconstructive surgery: a cohort study of 73 patients with a mean follow-up of 4.9 years

BackgroundPelvic and femoral osteotomies have been effective methods to treat developmental dysplasia of the hip (DDH), neurogenic dislocation of the hip (NDH), and Legg–Calvé–Perthes disease (LCPD). The aim of this study was to evaluate the mid-term results after hip reconstruction in children with DDH, NDH, and LCPD.MethodsIn a retrospective study, X-rays of 73 children (2–19 years) with DDH, NDH, and LCPD were measured before, 3 months, and at final follow-up (FU) after hip reconstructive surgery (open reduction, and femoral and/or pelvic osteotomy ± soft-tissue procedures between 2008 and 2018). Measurement of hip geometry included acetabular index (AI), center-edge angle (CE), and Reimers migration index (RMI). Mean follow-up time at final FU was 4.9 years. P value was set P < 0.05.ResultsAfter surgery (femoral osteotomy: 84 hips, Salter innominate osteotomy: 21 hips, Pemberton osteotomy: 30 hips, open reduction: 28 hips, Chiari osteotomy: 4 hips, and soft-tissue release: 24 hips), hip geometry parameters improved significantly. Nevertheless, at final FU, there was deterioration in hip geometry with femoral head lateralization (RMI) compared to the data at 3 months after surgery (RMI: preop/3 months/final FU: 40.6 ± 16.1%/6.1 ± 9.0/15.4 ± 16.0%; CE: 11.3° ± 20.0°/30.2° ± 9.5°/27.9 ± 15.4°; AI: 28.8° ± 9.6°/19.1° ± 7.6°/18.3 ± 7.6°). Sub-group analysis did not show differences concerning the progression of RMI in DDH, NDH, and LCPD at final FU. Regardless of basic disease, the lateralization was observed in all three groups (DDH, NDH, and LCPD) and statistically significant comparing X-rays 3 months postoperatively to maximum follow-up (DDH; NDH; LCPD: 2.7 ± 6.8%/7.6 ± 10.1%; 13.7 ± 15.3%/22.8 ± 19.8%; 1.7 ± 4.1%/14.9 ± 11.3%). Additional soft-tissue release techniques in patients with DDH or NDH did not show postoperative differences with statistical significance. Concerning surgical techniques, a connection between the lower RMI and the procedure of osteotomy of the ilium was found. In 25 patients, (34%) complications were observed: superficial skin lesions in 8, deep skin lesions in 3, contraction of adductors in 3, subluxation in 2, dislocations of the cast in 2, osteonecrosis of the femoral head in 2 cases, reluxation in 1, infection of the implanted plate in 1, compliance problem in 1, delayed bone healing in 1, and contraction of knee flexors in 1 case.DiscussionThe basic results of this study show a significant improvement of hip geometry at a follow-up of 4.9 years and prove findings of previously published literature. Moreover, the study was able to show a progression of RMI in all patient groups, which have undergone reconstructive surgery, despite basic hip geometry data (AI, CE angle) did not change. Those findings were independent from underlying pathology. Complications were counted in 34% of the patients and involved all known adverse events after hip reconstructive surgery. This makes clear why annual follow-up checks are needed not to miss the right indication for revision surgery.Clinical relevanceEvidence level: Level IV, case series.Trial registration: This manuscript is part of a prospective randomized clinical trial, registered in the German Clinical Trials Register DRKS-ID: DRKS00016861.

Hip Geometry Variation in Homozygous Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficient Patients

ENPP1 is an important regulator of skeletal and soft tissue mineralization. Mouse models have demonstrated a link between defective ENPP1 and altered bone mineralization, including osteopenia and mild osteomalacia. In humans, rare homozygous loss of ENPP1 leads to generalized arterial calcification of infancy (GACI), characterized by vascular, joint, and organ calcification, hypophosphatemic rickets/osteomalacia, and skin and retinal findings. Heterozygous ENPP1 deficiency has been described in early-onset osteoporosis and an ENPP1 polymorphism was found to be strongly associated with variation in hip geometry, as measured by DXA hip structural analysis (HSA). However, the overall skeletal phenotype of ENPP1-deficiency is not well characterized in affected individuals. In addition to bone density, DXA provides surrogate information about mechanical strength, resistance to compression, tension, and buckling, offering a non-invasive and clinically accessible tool to assess hip geometry. Parameters include cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), subperiosteal width (SPW), endocortical width (ECW), cortical thickness (CT), section modulus (Z), and buckling ratio (BR)—each measured in the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS) regions. SPW and ECW increase with age and are correlated with bone fragility. In mice, CSA and CSMI are inversely correlated with bone fragility when assessed by biomechanical tests. However, the opposite correlation has been observed in patients with fractures. HSA by DXA was assessed in 7 homozygous ENPP1-deficient patients (age range 5–56 years) and in 73 sex- and age-matched controls. All ENPP1-deficient patients were hypophosphatemic, of which, 2 were receiving treatment. Given the small sample size, standardized test statistics (t-scores) were derived for 21 hip geometry parameters; comparisons between groups were performed using the Mann-Whitney test. The Benjamini-Hochberg test was used to correct for multiple comparisons with a false discovery rate (FDR) q-value threshold set at 0.15. Compared with controls, ENPP1-deficient patients had significant changes in structural and derived measures of strength. Increases were seen in NN SPW, NN ECW, and FS SPW, which are correlated with bone fragility. In contrast, the increases seen in FS CSA, FS Z, FS CSMI, and NN CSMI are associated with improved bone strength. Although a q-value threshold of 0.15 indicates that 15% (~1/7) of all significant discoveries will represent a false positive, most findings represented true discoveries. These findings suggest that ENPP1 influences bone structure and strength, supporting findings from the aforementioned ENPP1 polymorphism study describing increased SPW in the NN and FS regions. This work contributes to the nascent body of literature studying the impact of ENPP1 on skeletal homeostasis.

Restoration of the hip geometry after two-stage exchange with intermediate resection arthroplasty for periprosthetic joint infection

Two-stage exchange with intermediate resection arthroplasty (RA) is a well-established surgical procedure in the treatment of chronic periprosthetic joint infection (PJI), whereby a higher failure rate of final hip geometry restoration due to tissue contraction is controversially discussed. The aim was to evaluate radiographic changes of hip geometry parameters during PJI treatment and to determine the impact of the intermediate RA on the final joint restoration after reimplantation of a total hip arthroplasty (reTHA). Radiographic parameters (leg length (LL), femoral offset (FO), horizontal/vertical acetabular center of rotation distance (h/vCORD)) of 47 patients (mean age: 64.1 years) were measured on standard radiographs of the pelvis and compared between four different stages during PJI treatment (pre-replacement status (preTHA), primary total hip arthroplasty (pTHA), RA and reTHA). The RA duration (mean: 10.9 months) and the number of reoperations during this period (mean: n = 2.0) as well as their impact on hip geometry restoration were evaluated. Between preTHA and pTHA/reTHA an equivalent restoration was measured regarding the FO (p < 0.001/p < 0.001) and hCORD (p = 0.016/p < 0.001), but not regarding the LL and vCORD. In contrast, analysis revealed no influence of RA and an equivalent reconstruction of LL (p = 0.003), FO (p < 0.001), v/hCORD (p = 0.039/p = 0.035) at reTHA compared to pTHA. Furthermore, RA duration (p = 0.053) and the number of reoperations after RA (p = 0.134) had no impact on radiographic hip geometry restoration. The two-stage exchange with intermediate RA does not alter the preexisting hip joint parameters, whereby a good restoration of the final hip geometry, independent of the duration or the number of reoperations, can be achieved.

Newly developed hip geometry parameters are associated with hip fracture

BackgroundThe conventional and newly developed geometry parameters at the femoral neck have formed a large geometry profile and their relationship with hip fracture was largely unknown. We aimed to evaluate the relationship between the geometry profile and hip fracture in Chinese. MethodsThe hip geometry profile contains seven conventional geometry parameters at femoral neck (FN) and thirty newly developed parameters at three sub-regions (Narrow Neck, NN; Intertrochanter, IT; Femoral shaft, FS) of the total hip. Based on 6294 recruited Chinese (≥65 years), 97 subjects with osteoporotic fracture (OF) history and 388 matched controls were selected. The t test, Chi-square statistic, conditional logistic regression model were used. ResultsThree geometric parameters (endocortical diameter, ED; cortical thickness, CT; buckling ratio, BR) have consistent differences at all the sites between the cases and controls (p < 0.01). Conventional geometry parameters (e.g., cross-sectional area, CSA; BR) and the newly developed parameters (e.g., NN_ED, NN_Outer Diameter, IT_ED) were identified as the risk factors of hip fracture independent of BMD. The additional predictive ability of the hip geometric parameters, over BMD alone, (receiver operating characteristic curve (ROC) analysis) was improved. Especially at NN, the area of ROC used single NN_BMD is only 0.596, but increased rapidly at 0.705 when combined with the hip geometric parameters. ConclusionsThis study found that three newly developed hip geometry parameters are associated with hip fracture. The results will increase our understanding of the determinants of fracture and provide potential clue for future prevention of fracture in Chinese Population.

Influence of sarcopenia on bone health parameters in a group of eumenorrheic obese premenopausal women.

The aim of this study was to compare bone mineral density (BMD) and geometric indices of hip bone strength in a group of obese sarcopenic premenopausal women (n = 27) and a group of obese premenopausal women with normal appendicular lean mass (ALM)/body mass index ratio (BMI) (n = 26). The ALM/BMI criterion of The Foundation for the National Institute of Health was used; women with an ALM/BMI ratio < 0.512m2 were considered obese sarcopenic. Body composition and bone variables were measured by DXA. DXA measurements were completed for the whole body (WB), lumbar spine (L1-L4), total hip (TH) and femoral neck (FN). Hip geometry parameters including cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), strength index (SI) and buckling ratio (BR) were derived by DXA. Age, weight and BMI were not significantly different between the two groups. Height, lean mass, skeletal muscle mass index, ALM and the ratio ALM/BMI were significantly higher in obese women with normal ALM/BMI ratio compared to obese sarcopenic women. Fat mass percentage was significantly higher in obese sarcopenic women compared to obese women with normal ALM/BMI ratio. WB BMC, TH BMD, FN BMD, CSA, CSMI and Z were significantly higher in obese women with normal ALM/BMI ratio compared to obese sarcopenic women. In the whole population (n = 53), ALM and the ratio ALM/BMI were positively correlated to WB BMC, CSA, CSMI and Z. The present study suggests that sarcopenia negatively influences bone mineral density and hip geometry parameters before menopause in eumenorrheic obese women.

Influence of Hip Geometry Reconstruction on Frontal Plane Hip and Knee Joint Moments During Walking Following Primary Total Hip Replacement

BackgroundFollowing total hip replacement (THR), hip geometry reconstruction parameters such as the femoral offset (FO) correlate with hip stability and wear. The purpose of this study is to determine the relationship between hip geometry parameters and knee and hip joint loading during walking. MethodsForty-one patients were examined before and a minimum of 1 year after primary THR. Pearson correlation coefficient (r) was performed to identify relationships between radiographic parameters and gait data. In addition, we divided patients into 2 groups according to the restoration of the FO (within ±5 mm vs more than 5 mm increment). ResultsThe FO and global offset (GO) showed a positive correlation with the first (r = 0.469, P = .002; r = 0.542, P < .001) and second (r = 0.365, P = .019; r = 0.484, P = .001) knee adduction moment (KAM). The neck-shaft angle revealed a negative correlation with the first hip adduction moment (r = −0.375, P = .047). The reconstruction of FO with an increment of more than 5 mm was associated with a significant higher first KAM (+16%, P = .045) compared to the restored group. ConclusionOur findings suggest that abnormal hip and knee joint loading during walking after THR have a biomechanical background originating from hip geometry reconstruction. Patients with a high FO/GO were more likely to have an increased KAM during walking or vice versa. Surgeons need to be aware that an accurate control of FO, GO, and neck-shaft angle restoration in THR has an impact on hip and knee joint loading that may influence degenerative changes of the knee and higher wear of the artificial hip joint, respectively.

Evaluation of Hip Geometry Parameters in Patients With a Distal Radius Fracture

Background: Patients with a distal radius fracture (DRF) have an increased risk of subsequent fractures including hip fractures. The purpose of this study was to evaluate whether women with a DRF have certain hip geometry parameters known to indicate susceptibility to hip fractures. Methods: We compared bone mineral density (BMD) and hip geometry parameters (hip axis length, neck shaft angle, mean cortical thickness, femur neck width, cross-sectional area [CSA], cross-sectional moment of inertia, section modulus, and buckling ratio) in 181 women with a DRF (DRF group) and 362 propensity score-matched women without a fracture (control group). We evaluated the associations between DRF and hip geometry parameters using logistic regression analysis. Results: The DRF group had lower hip BMD; lower cortical thickness, CSA, and section modulus; and higher buckling ratio than the control group (all p < 0.05). The occurrence of a DRF was significantly associated with decreases in neck shaft angle (odds ratio [OR], 1.047; 95% confidence interval [CI], 1.008–1.088) and CSA (OR, 3.114; 95% CI, 1.820–5.326) after adjusting for age, BMI, and total hip BMD. Conclusions: In this study, women with a DRF were more likely than women without a DRF to have hip geometry parameters known to indicate susceptibility to hip fractures. Our results suggest that not only low hip BMD but also a decreased CSA could account for the increased risk of subsequent hip fracture in patients with a DRF.

Relationship of calf circumference with bone mineral density and hip geometry: a hospital-based cross-sectional study.

Calf circumference has significant predictive value for bone mineral density (BMD) at hip and spine and for fracture at spine in both genders and hence may be used as a clinical risk factor for fracture when BMD is not available. Lean muscle mass and higher regular physical ability has been shown to correlate with BMD and hip geometry. Calf circumference is an indicator of muscle mass. We examined the association of calf circumference (CC), thigh circumference (TC), and physical performances with BMD and hip geometry. Females above 45 years (at least 5 years postmenopausal) and males above 55 years were enrolled. Bilateral CC and TC were measured, and BMD was assessed at neck of femur (NF), trochanter (TR), inter-trochanter (IT), spine, and forearm. Dual energy X-ray absorptiometry scan-based hip geometry parameters were analyzed. One hundred sixteen subjects (29 males and 87 females) were enrolled. CC correlated significantly with BMD at NF, IT, TR, and spine in male and female, respectively, and at forearm in female. Multivariate regression analysis showed CC as a significant predictor of BMD (at TR, IT, NF, and spine in both genders) and fracture (at spine in both genders). CC had significant positive correlation with hip parameters-cross-sectional area; cortical thickness; and section modulus at NF, IT, and TR in both genders and negative correlation with buckling ratio at NF and IT in females. CC is a significant predictor of BMD at hip and spine and fracture at spine in both genders.

Sex-specific differences in progressive glucose intolerance and hip geometry: the Baltimore Longitudinal Study of Aging.

Fracture risk is increased in type 2 diabetes mellitus (T2DM). The effect of pre-diabetes and T2DM on bone macroarchitecture and strength has not been well investigated. In this study, we show that in women only, both pre-diabetes and T2DM are associated with decreased hip bending strength and mineralization which might lead to skeletal weakness. Older men and women with T2DM are at increased risk for fracture despite normal bone mineral density (BMD). The discordance between bone quantity and skeletal fragility has driven investigation into additional determinants of fracture resistance in T2DM. Additionally, the effect of pre-diabetes on bone strength has not been well described. The aim of this study was to determine differences in bone macroarchitecture and strength, measured by hip geometry, in persons with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. We performed cross-sectional analyses of older (age >55years) men (n = 472) and women (n = 473) participating in the Baltimore Longitudinal Study of Aging (BLSA) classified as NGT, IGT, or T2DM based on oral glucose tolerance testing. Bone strength measures included the hip geometry parameters of section modulus (Z), cross-sectional area (CSA), and buckling ratio (BR). Sex-stratified analyses were conducted using adjusted stepwise regression models. In women, IGT and T2DM were negatively associated with hip geometry parameters including mineralization in cross section (CSA, ß -0.076 and -0.073, respectively; both p < 0.05) and hip bending strength (Z, ß -0.097 and -0.09, respectively; both p < 0.05); conversely, IGT and T2DM were associated with improved compressive strength (BR, ß -0.31 and -0.29, respectively; both p < 0.05). There was no significant association between glycemic status and hip geometry in men. In women only, both IGT and T2DM were inversely associated with bone macroarchitecture and measures of bone mineralization and bending strength. The same association between worsening glycemic status and bone strength was not observed in men. These data suggest a differential effect of sex on hip geometry with evolving glucose intolerance.

A common LRP4 haplotype is associated with bone mineral density and hip geometry in men—Data from the Odense Androgen Study (OAS)

Osteoporosis is a common disease characterized by an increased susceptibility to fracture. It is a complex disorder resulting from the interaction of several polymorphisms in different genes and environmental factors. Since we recently reported a role for low density lipoprotein-related protein (LRP)-4 in monogenic disorders with bone overgrowth, we now wanted to evaluate whether genetic variation in the LRP4 gene has an effect on the susceptibility to osteoporosis in a population based cohort from the Odense Androgen Study. We chose to genotype four common (minor allele frequency (MAF)≥0.05) and non-synonymous coding polymorphisms located in the extracellular region of the LRP4 protein: rs3816614 (A/g), rs2306029 (G/a), rs2306033 (C/t) and rs6485702 (G/a) (large and small characters indicate major and minor alleles, respectively). Bone mineral density (BMD) measurements of the hip, the spine and whole body as well as different hip geometry parameters were available for a total of 1404 Danish men from two age groups ([20–29 years]: n=804; [60–74 years]: n=600). Using linear regression analysis adjusted for age, height and weight, we found significant associations between both rs2306029 and rs6485702 and BMD at all sites except the lumbar spine. The most significant association was found with whole body BMD (p=4.7×10−5). In addition, we found these two polymorphisms to be associated with different geometry parameters especially of the femoral shaft. Analysis of the two associated SNPs in the separate age groups demonstrated that most associations are only present in the youngest group of Danish men. In the group of elderly men, one Bonferroni corrected association between whole body BMD and rs6485702 was found to be significant. Subsequently, all polymorphisms were included in haplotype analyses using the PLINK software (v1.07). After adjusting for age, height and weight, two out of five common haplotypes (MAF≥0.01) were found to be of particular interest in the regulation of hip and whole body BMD (AGCG, AACA). Additional analysis suggested that these latter associations are driven by the association of rs6485702. We suggest, based on these results and the localisation of the variant in the third β-propeller domain of LRP4, that the variant has possibly a functional effect. Hereby, we conclude that common variation in the LRP4 gene determines hip and whole body BMD and thus confirm previous results from different GWAs. In addition, our data proves an additional role for LRP4 in regulating hip structure. Finally, interaction analysis for LRP4 with SOST and LRP5 showed interaction with LRP5 for femoral shaft geometry.

Single nucleotide polymorphisms in sFRP4 are associated with bone and body composition related parameters in Danish but not in Belgian men

The senescence accelerated mouse P6 (SAMP6) has a low bone mass and has previously shown to be a good model for senile osteoporosis in humans. In addition to a reduced bone mass, SAMP6 mice are obese and have hyperlipidemia. Using positional cloning and expression studies, an increased expression of sfrp4 was found in these mice. SFRP4 is a modulator of the Wnt signalling pathway. This pathway has been previously shown to be involved in regulating bone mass. Additional evidence that sFRP4 has an influence on BMD was delivered by linkage and association studies mostly performed in Asian populations. Based on these data we decided to perform an association study between common variants in sFRP4, BMD, hip geometry parameters and body composition parameters in a population consisting of 1383 Danish men (783 aged 20–29years; 600 aged 60–74years). Afterwards we tried to replicate the significant results in a population of 994 Belgian men.In the Danish population we found 6 SNPs associated with BMD at the hip and/or femoral neck. Furthermore, all 6 SNPs were associated with several hip geometry parameters. The homozygous presence of the minor allele resulted for all SNPs (except rs4720265) in a decrease in bone density and bone strength. Finally, we observed in the Danish population age specific associations with height and fat mass. In the Belgian population we tried to replicate the results of three SNPs with BMD and body composition parameters. Unfortunately, we were not able to replicate the results found in the Danish cohort but we found one SNP (rs2598116) associated with height.In conclusion, genetic variation in sFRP4 has an influence on hip fracture risk, percentage body fat and height in a Danish male population. However, we were unable to replicate these results in an independent Belgian population.

Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training

We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. A total of 107 obese (body mass index [BMI] ≥ 30 kg/m(2)) older (≥65 years) adults were randomly assigned to control, diet, exercise, and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6 months, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy X-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (-9.6% and -9.4%, respectively), whereas weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6% ± 1.7% and 10.5% ± 1.9% at 6 and 12 months, respectively, all p < 0.05), whereas they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7% ± 1.6% and 0.4% ± 1.7% at 6 and 12 months, respectively, all p = 0.05). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (p < 0.05). In conclusion, the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training.

Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts

Bone mineral density (BMD) and bone strength are predictive parameters for the development of osteoporosis and related fracture later in life. Although it is well known that BMD and bone strength have a high heritability, not much of the variation is already explained. Mice models showed that sFRP1 has an influence on bone formation. Therefore this study aimed to investigate the effect of common genetic variation on BMD and bone strength in Caucasian men of different ages.Using HapMap we selected 13 tagSNPs which tag most common genetic variation in and around sFRP1 and we genotyped these SNPs in the young cohort of the Odense Androgen Study (OAS). The OAS includes a total of 1383 Danish men from two different age groups ([20–29years]: N=783; [60–74years]: N=600) and is well characterised. The subjects were phenotyped for BMD at several sites, and additionally for body composition and hip geometry parameters. Based on the results of the young cohort we selected three SNPs for further analysis in the complete OAS population. To conclude we tried to replicate the results of two SNPs in an independent population of 994 Belgian men.We found a strong association for rs9694405 with BMI as well in both cohorts separately as in the whole OAS population. Further we found rs4736965 associated with several hip geometry parameters in the same population. However we were not able to replicate those results in the Belgian population. At last we found in the OAS population age specific effects for rs10106678 with whole body BMD and waist to hip ratio.

Lean Mass Predicts Hip Geometry in Men and Women With Non–Insulin-Requiring Type 2 Diabetes Mellitus

Persons with type 2 diabetes mellitus (T2DM) are at increased risk for hip fracture despite normal bone mineral density (BMD). The contribution of body composition to hip geometry, a measure of hip strength, has not been studied in T2DM. We hypothesized that lean mass would predict hip geometry. Subjects (n = 134) for this cross-sectional analysis were men and women aged 56 ± 6 yr with non–insulin-requiring T2DM. Fat and lean mass were measured with dual-energy X-ray absorptiometry (DXA). Abdominal fat was measured with magnetic resonance imaging. Hip geometry parameters including section modulus, cross-sectional area, and buckling ratio were estimated from DXA using validated formulae. Subjects had normal BMD, elevated body mass indices (29–41 kg/m 2), and controlled T2DM (hemoglobin A1c: 5.1–8.3%). In bivariate analysis, lean mass was positively associated with section modulus and cross-sectional area in both sexes ( r = 0.36–0.55, p < 0.05). In multivariate analyses, lean mass remained a significant predictor of all hip strength estimates in both sexes. In women alone, fat mass predicted parameters of hip strength. These data demonstrate that lean mass is significantly associated with hip strength in subjects with non–insulin-requiring T2DM. Resistance exercises that build lean mass may be an intervention for hip fracture prevention in T2DM, although additional research is needed.

Genetic variation in secreted frizzled related protein 4 (sFRP4) is associated with femoral neck BMD and hip geometry parameters in Danish men — Results from the Odense Androgen Study

Genetic variation in secreted frizzled related protein 4 (sFRP4) is associated with femoral neck BMD and hip geometry parameters in Danish men — Results from the Odense Androgen Study