Prediction Of Hip Fracture Risk Research Articles

The influence of the modulus–density relationship and the material mapping method on the simulated mechanical response of the proximal femur in side-ways fall loading configuration

Contributing to slow advance of finite element (FE) simulations for hip fracture risk prediction, into clinical practice, could be a lack of consensus in the biomechanics community on how to map properties to the models. Thus, the aim of the present study was first, to systematically quantify the influence of the modulus–density relationship (E–ρ) and the material mapping method (MMM) on the predicted mechanical response of the proximal femur in a side-ways fall (SWF) loading configuration and second, to perform a model-to-model comparison of the predicted mechanical response within the femoral neck for all the specimens tested in the present study, using three different modelling techniques that have yielded good validation outcome in terms of surface strain prediction and whole bone response according to the literature. We found the outcome to be highly dependent on both the E–ρ relationship and the MMM. In addition, we found that the three modelling techniques that have resulted in good validation outcome in the literature yielded different principal strain prediction both on the surface as well as internally in the femoral neck region of the specimens modelled in the present study. We conclude that there exists a need to carry out a more comprehensive validation study for the SWF loading mode to identify which combination of MMMs and E–ρ relationship leads to the best match for whole bone and local mechanical response. The MMMs tested in the present study have been made publicly available at https://simtk.org/home/mitk-gem.

Genetic Contribution of Femoral Neck Bone Geometry to the Risk of Developing Osteoporosis: A Family-Based Study.

Femoral neck geometry parameters are believed to be as good as bone mineral density as independent factors in predicting hip fracture risk. This study was conducted to analyze the roles of genetic and environmental factors in femoral properties measured in a sample of Spanish families with osteoporotic fractures and extended genealogy. The “Genetic Analysis of Osteoporosis (GAO) Project” involved 11 extended families with a total number of 376 individuals. We studied three categorical phenotypes of particular clinical interest and we used a Hip structural analysis based on DXA to analyze 17 strength and geometrical phenotypes of the hip. All the femoral properties had highly significant heritability, ranging from 0.252 to 0.586. The most significant correlations were observed at the genetic level (ρG). Osteoporotic fracture status (Affected 2) and, particularly, low bone mass and osteoporotic condition (Affected 3) had the highest number of significant genetic correlations with diverse femoral properties. In conclusion, our findings suggest that a relatively simple and easy to use method based on DXA studies can provide useful data on properties of the Hip in clinical practice. Furthermore, our results provide a strong motivation for further studies in order to improve the understanding of the pathophysiological mechanism underlying bone architecture and the genetics of osteoporosis.

Associations of Age, BMI, and Years of Menstruation with Proximal Femur Strength in Chinese Postmenopausal Women: A Cross-Sectional Study.

This study aimed to elucidate the associations of age, BMI, and years of menstruation with proximal femur strength in Chinese postmenopausal women, which may improve the prediction of hip fracture risk. A cross-sectional study was conducted in 1322 Chinese postmenopausal women recruited from communities. DXA images were used to generate bone mineral density (BMD) and geometric parameters, including cross-sectional area (CSA), outer diameter (OD), cortical thickness (CT), section modulus (SM), buckling ratio (BR) at the narrow neck (NN), intertrochanter (IT), and femoral shaft (FS). Relationships of age, BMI, and years of menstruation with bone phenotypes were analyzed with the adjustment of height, age at menarche, total daily physical activity, education, smoking status, calcium tablet intake, etc. Age was associated with lower BMD, CSA, CT, SM, and higher BR (p < 0.05), which indicated a weaker bone strength at the proximal femur. BMI and years of menstruation had the positive relationships with proximal femur strength (p < 0.05). Further analyses showed that the ranges of absolute value of change slope per year, per BMI or per year of menstruation were 0.14%–1.34%, 0.20%–2.70%, and 0.16%–0.98%, respectively. These results supported that bone strength deteriorated with aging and enhanced with higher BMI and longer time of years of menstruation in Chinese postmenopausal women.

Bone turnover biomarkers and risk of osteoporotic hip fracture in an Asian population

While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case–control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45–74years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), N-terminal and C-terminal crosslinking telopeptide of type I collagen (NTX-I and CTX-I) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, PINP, CTX-I and NTX-I than controls (p<0.05). There was a dose-dependent positive relationship between OC, PINP, CTX-I and NTX-I and risk of hip fracture (all Ps for trend≤0.006), where the risk was significantly increased by 4.32–8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% CI)] at the highest quartile (Q4) was 6.63 (2.02–21.18) for PINP and 4.92 (1.67–14.51) for CTX-I. The joint effect of PINP and CTX-I showed a 7-fold increase in risk (OR: 7.36; 95% CI: 2.53–21.41) comparing participants with higher levels of PINP (Q4) and CTX-I (Q3–Q4) to those with low levels of PINP (Q1–Q3) and CTX-I (Q1–Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population.

Fusion of clinical and stochastic finite element data for hip fracture risk prediction

Hip fracture affects more than 250,000 people in the US and 1.6 million worldwide per year. With an aging population, the development of reliable fracture risk models is therefore of prime importance. Due to the complexity of the hip fracture phenomenon, the use of clinical data only, as it is done traditionally, might not be sufficient to ensure an accurate and robust hip fracture prediction model. In order to increase the predictive ability of the risk model, the authors propose to supplement the clinical data with computational data from finite element models. The fusion of the two types of data is performed using deterministic and stochastic computational data. In the latter case, uncertainties in loading and material properties of the femur are accounted for and propagated through the finite element model. The predictive capability of a support vector machine (SVM) risk model constructed by combining clinical and finite element data was assessed using a Women׳s Health Initiative (WHI) dataset. The dataset includes common factors such as age and BMD as well as geometric factors obtained from DXA imaging. The fusion of computational and clinical data systematically leads to an increase in predictive ability of the SVM risk model as measured by the AUC metric. It is concluded that the largest gains in AUC are obtained by the stochastic approach. This gain decreases as the dimensionality of the problem increases: a 5.3% AUC improvement was achieved for a 9 dimensional problem involving geometric factors and weight while a 1.3% increase was obtained for a 20 dimensional case including geometric and conventional factors.

Overdiagnosis and Overtreatment of Osteoporosis: A Wolf in Sheep's Clothing.

Overdiagnosis and Overtreatment of Osteoporosis: A Wolf in Sheep's Clothing.

TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association.

Chronic inflammation may increase the risk of fracture, and omega-3 polyunsaturated fatty acids (PUFAs) may reduce fracture risk via down-regulation of inflammatory cytokine gene expression and other mechanisms. We investigated associations between baseline samples of inflammatory markers, TNFα soluble receptors 1 and 2 (TNFα-sR1 and -sR2), and incident hip fracture. These associations were then tested for effect modification by dietary PUFA intake estimated by a baseline food frequency questionnaire. A nested case-control study was conducted among participants of the Women's Health Initiative Observational Study (ages, 50-79 y). Multivariable conditional logistic regression models were constructed to account for the paired design. This study sampled 400 pairs of hip fracture cases and controls without incident hip fracture, matched on age, year of enrollment, and menopausal hormone use. Odds ratio of hip fracture by quartile of TNF soluble receptors. The odds ratio of hip fracture comparing the highest to lowest quartiles was 2.24 (95% confidence interval, 1.05-4.79; P for linear trend, .048) for TNFα-sR1 and 2.83 (95% confidence interval, 1.34-5.99; P for linear trend, .011) for TNFα-sR2, adjusted for FRAX hip fracture score, nutritional variables, and selected factors impacting inflammation; there was a gradient of risk by increasing quartile in TNFα-sR1. PUFA intake did not modify these associations. Women with the highest levels of TNFα-sR1 and TNFα-sR2 had a greater than 2-fold increased hip fracture risk, independent of other fracture risk factors. These associations did not differ by high vs low PUFA intake.

Generation of 3D shape, density, cortical thickness and finite element mesh of proximal femur from a DXA image.

Areal bone mineral density (aBMD), as measured by dual-energy X-ray absorptiometry (DXA), predicts hip fracture risk only moderately. Simulation of bone mechanics based on DXA imaging of the proximal femur, may help to improve the prediction accuracy. Therefore, we collected three (1-3) image sets, including CT images and DXA images of 34 proximal cadaver femurs (set 1, including 30 males, 4 females), 35 clinical patient CT images of the hip (set 2, including 27 males, 8 females) and both CT and DXA images of clinical patients (set 3, including 12 female patients). All CT images were segmented manually and landmarks were placed on both femurs and pelvises. Two separate statistical appearance models (SAMs) were built using the CT images of the femurs and pelvises in sets 1 and 2, respectively. The 3D shape of the femur was reconstructed from the DXA image by matching the SAMs with the DXA images. The orientation and modes of variation of the SAMs were adjusted to minimize the sum of the absolute differences between the projection of the SAMs and a DXA image. The mesh quality and the location of the SAMs with respect to the manually placed control points on the DXA image were used as additional constraints. Then, finite element (FE) models were built from the reconstructed shapes. Mean point-to-surface distance between the reconstructed shape and CT image was 1.0 mm for cadaver femurs in set 1 (leave-one-out test) and 1.4 mm for clinical subjects in set 3. The reconstructed volumetric BMD showed a mean absolute difference of 140 and 185 mg/cm(3) for set 1 and set 3 respectively. The generation of the SAM and the limitation of using only one 2D image were found to be the most significant sources of errors in the shape reconstruction. The noise in the DXA images had only small effect on the accuracy of the shape reconstruction. DXA-based FE simulation was able to explain 85% of the CT-predicted strength of the femur in stance loading. The present method can be used to accurately reconstruct the 3D shape and internal density of the femur from 2D DXA images. This may help to derive new information from clinical DXA images by producing patient-specific FE models for mechanical simulation of femoral bone mechanics.

A two-level subject-specific biomechanical model for improving prediction of hip fracture risk

BackgroundSideways fall-induced hip fracture is a major worldwide health problem among the elderly population. However, all existing biomechanical models for predicting hip fracture mainly consider the femur related parameters. Their accuracy is limited as hip fracture is significantly affected by loading conditions as well. The objective of this study was to develop a biomechanical model for improving assessment of hip fracture risk by subject-specific prediction of fall-induced loading conditions. MethodAll information required to construct the models was extracted from the subject's whole-body and hip medical image in order to make the models subject-specific. Fall-induced hip fracture risk for eighty clinical cases was calculated under two sets of loading conditions: subject-specific determined by the proposed model, and non-subject-specific obtained from empirical functions. The predicted hip fracture risk indices were then compared with clinical observations. FindingsIt was found that the subject-specific prediction of fall-induced loading conditions significantly improves the hip fracture risk assessment. Consistent to the clinical observations, the fracture risk predicted by the proposed model suggested that obesity is a protective factor for hip fracture and underweight subjects are more likely to experience a hip fracture. InterpretationsThis study shows that hip fracture risk is affected by a number of factors, including body weight, body height, impact force, body mass index, hip soft tissue thickness, and bone quality. The proposed model provides a comprehensive, fast, accurate, and non-expensive method for prediction of hip fracture risk which should lead to more effective prevention of hip fractures.

Study of DXA-derived lateral–medial cortical bone thickness in assessing hip fracture risk

The currently available clinical tools have limited accuracy in predicting hip fracture risk in individuals. We investigated the possibility of using normalized cortical bone thickness (NCBT) estimated from the patient's hip DXA (dual energy X-ray absorptiometry) as an alternative predictor of hip fracture risk. Hip fracture risk index (HFRI) derived from subject-specific DXA-based finite element model was used as a guideline in constructing the mathematical expression of NCBT. We hypothesized that if NCBT has stronger correlations with HFRI than the single risk factors such as areal BMD (aBMD), then NCBT can be a better predictor. The hypothesis was studied using 210 clinical cases, including 60 hip fracture cases, obtained from the Manitoba Bone Mineral Density Database. The results showed that, in general HFRI has much stronger correlations with NCBT than any of the single risk factors; the strongest correlation was observed at the superior side of the narrowest femoral neck with r2=0.81 (p<0.001), which is much higher than the correlation with femoral aBMD, r2=0.50 (p<0.001). The capability of aBMD, NCBT, and HFRI in discriminating the hip fracture cases from the non-fracture ones, expressed as the area under the curve with 95% confidence interval, AUC (95% CI), is respectively 0.627 (0.593–0.657), 0.714 (0.644–0.784) and 0.839 (0.787–0.892). The short-term repeatability of aBMD, NCBT, and HFRI, measured by the coefficient of variation (CV, %), was found to be in the range of (0.64–1.22), (1.93–3.41), (3.10–4.16), respectively. We thus concluded that NCBT is potentially a better predictor of hip fracture risk.

Assessment of Hip Fracture Risk Using Cross-Section Strain Energy Determined by QCT-Based Finite Element Modeling

Accurate assessment of hip fracture risk is very important to prevent hip fracture and to monitor the effect of a treatment. A subject-specific QCT-based finite element model was constructed to assess hip fracture risk at the critical locations of femur during the single-leg stance and the sideways fall. The aim of this study was to improve the prediction of hip fracture risk by introducing a novel failure criterion to more accurately describe bone failure mechanism. Hip fracture risk index was defined using cross-section strain energy, which is able to integrate information of stresses, strains, and material properties affecting bone failure. It was found that the femoral neck and the intertrochanteric region have higher fracture risk than other parts of the femur, probably owing to the larger content of cancellous bone in these regions. The study results also suggested that women are more prone to hip fracture than men. The findings in this study have a good agreement with those clinical observations reported in the literature. The proposed hip fracture risk index based on strain energy has the potential of more accurate assessment of hip fracture risk. However, experimental validation should be conducted before its clinical applications.

DXA Subcutaneous Fat Thickness and Cross-Sectional Muscle Area Predict Hip Fracture Risk Independent of Hip BMD in Older Adults

DXA Subcutaneous Fat Thickness and Cross-Sectional Muscle Area Predict Hip Fracture Risk Independent of Hip BMD in Older Adults

Association between fat‐mass‐and‐obesity‐associated (FTO) gene and hip fracture susceptibility

Common variants in the fat-mass-and-obesity-associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk. This is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study), followed up between 1989 and 2007. Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the follow-up was ascertained by reviewing X-ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association. One hundred and two women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNPs. Women homozygous for the minor allele (AA) of rs1121980 had significantly higher risk of hip fracture (hazard ratio, 2.06; 95% CI 1.17-3.62) than women homozygous for the major allele (TT). The observed data favoured the hypothesis of FTO gene and fracture association over the hypothesis of nonassociation by a factor of nine. Common variations in the FTO gene are associated with hip fracture risk in women and that FTO gene may help improve the predictive value of hip fracture risk.

Estimated GFR and Risk of Hip Fracture in Older Men: Comparison of Associations Using Cystatin C and Creatinine

Higher serum cystatin C level is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data for men. Whether estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to eGFR based on creatinine (eGFRcr) or the combination (eGFR(cr-cys)) also is uncertain. Nested case-cohort. Participants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥ 65 years from 6 US centers) including a random subcohort of 1,602 men and 168 men with incident hip fractures (51 of whom were in the subcohort). eGFR(cys), eGFR(cr), and eGFR(cr-cys) computed using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and expressed in categories of <60, 60-74, and ≥ 75 mL/min/1.73 m(2) (referent group). Incident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports. Median eGFR(cys) was 72.9 (IQR, 60.5-85.7) mL/min/1.73 m(2). In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site, and body mass index, the association of lower eGFR(cys) (but not lower eGFR(cr) or lower eGFR(cr-cys)) with higher hip fracture risk remained: for <60 versus ≥ 75 mL/min/1.73 m(2), HRs were 1.96 [95% CI, 1.25-3.09], 0.84 [95% CI, 0.52-1.37], and 1.08 [95% CI, 0.66-1.77] for eGFR(cys), eGFR(cr), and eGFR(cr-cys), respectively. Similarly, after adjustment for age, race, site, and body mass index, eGFR < 60 mL/min/1.73 m(2) defined by eGFR(cys), but not eGFR(cr) or eGFR(cr-cys), was associated with higher hip fracture risk. The association between eGFR(cys) and hip fracture was not explained by levels of calciotropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs ≥ 75 mL/min/1.73 m(2): HR, 1.43; 95% CI, 0.88-2.34) after consideration of additional clinical risk factors and bone mineral density. Findings not generalizable to other populations; residual confounding may exist. Older community-dwelling men with lower eGFR(cys) have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFR(cys). In contrast, lower eGFR(cr) or lower eGFR(cr-cys) was not associated with a higher age-adjusted hip fracture risk.

THU0391 Is there a Relationship between Hip Structural Analysis and Bone Mineral Density at the Hip and Spine?

BackgroundHip structural analysis (HSA) has been suggested as possible method of improving prediction of hip fracture risk above that provided by current bone mineral density (BMD) use alone. To our...

Quantitative ultrasound measurements and vitamin D status in the assessment of hip fracture risk in a nationally representative population sample

Adjusted for age, gender, height and weight, calcaneal quantitative ultrasound (QUS) and serum 25-hydroxyvitamin D (S-25(OH)D) proved to be significant predictors of hip fracture among subjects aged ≥50 years. Even if their contribution to the predictive power was modest, they may be useful in the assessment of hip fracture risk in the elderly. This study assessed calcaneal QUS measurements, S-25(OH)D and several other factors for the prediction of hip fracture risk in a nationally representative population sample. The study population consisted of 3,305 subjects (1,872 women), aged 50 years or over, who had participated in a comprehensive health survey. QUS measurements were made by means of the Hologic Sahara device. S-25(OH)D was measured by radioimmunoassay. Emerging cases of hip fracture were identified from the National Hospital Discharge Register. During a mean follow-up of 8.4 years, 95 subjects sustained a hip fracture. After adjusting for age, gender, height, weight and each other, a 1 standard deviation increment in the quantitative ultrasound index (QUI) (21.7) and in S-25(OH)D (17.5 nmol/L) reduced the risk of hip fracture by 40 % (hazard ratio [HR] = 0.60, 95 % confidence interval [CI] = 0.42-0.86) and by 31 % (HR = 0.69, 95 % CI = 0.55-0.87), respectively. The predictive power of a model including age, gender, height and weight was improved by about 8 % after the addition of QUI and S-25(OH)D. Among subjects aged 75 years or over, the corresponding improvement was about 130 %. QUI and S-25(OH)D were significant and independent predictors of hip fracture. However, their ability to increase the predictive power of a statistical model including readily available simple variables such as age, gender, height and weight was rather modest. Still, our findings suggest that QUI and S-25(OH)D may be of clinical use in the assessment of hip fracture risk particularly in the elderly.

Bivariate Genome-Wide Association Analyses Identified Genes with Pleiotropic Effects for Femoral Neck Bone Geometry and Age at Menarche

Femoral neck geometric parameters (FNGPs), which include cortical thickness (CT), periosteal diameter (W), buckling ratio (BR), cross-sectional area (CSA), and section modulus (Z), contribute to bone strength and may predict hip fracture risk. Age at menarche (AAM) is an important risk factor for osteoporosis and bone fractures in women. Some FNGPs are genetically correlated with AAM. In this study, we performed a bivariate genome-wide association study (GWAS) to identify new candidate genes responsible for both FNGPs and AAM. In the discovery stage, we tested 760,794 SNPs in 1,728 unrelated Caucasian subject, followed by replication analyses in independent samples of US Caucasians (with 501 subjects) and Chinese (with 826 subjects). We found six SNPs that were associated with FNGPs and AAM. These SNPs are located in three genes (i.e. NRCAM, IDS and LOC148145), suggesting these three genes may co-regulate FNGPs and AAM. Our findings may help improve the understanding of genetic architecture and pathophysiological mechanisms underlying both osteoporosis and AAM.

Digital X-rays of wrist bones predict hip fracture risk

Digital X-rays of wrist bones predict hip fracture risk

Digital X-ray radiogrammetry of hand or wrist radiographs can predict hip fracture risk--a study in 5,420 women and 2,837 men.

ObjectivesTo assess whether digital X-ray radiogrammetry (DXR) analysis of standard clinical hand or wrist radiographs obtained at emergency hospitals can predict hip fracture risk.MethodsA total of 45,538 radiographs depicting the left hand were gathered from three emergency hospitals in Stockholm, Sweden. Radiographs with insufficiently included metacarpal bone, fractures in measurement regions, foreign material or unacceptable positioning were manually excluded. A total of 18,824 radiographs from 15,072 patients were analysed with DXR, yielding a calculated BMD equivalent (DXR-BMD). Patients were matched with the national death and inpatient registers. Inclusion criteria were age ≥ 40 years, no prior hip fracture and observation time > 7 days. Hip fractures were identified via ICD-10 codes. Age-adjusted hazard ratio per standard deviation (HR/SD) was calculated using Cox regression.Results8,257 patients (65.6 % female, 34.4 % male) met the inclusion criteria. One hundred twenty-two patients suffered a hip fracture after their radiograph. The fracture group had a significantly lower DXR-BMD than the non-fracture group when adjusted for age. The HR/SD for hip fracture was 2.52 and 2.08 in women and men respectively. The area under the curve was 0.89 in women and 0.84 in men.ConclusionsDXR analysis of wrist and hand radiographs obtained at emergency hospitals predicts hip fracture risk in women and men.Key Points• Digital X-ray radiogrammetry of emergency hand/wrist radiographs predicts hip fracture risk. • Digital X-ray radiogrammetry (DXR) predicts hip fracture risk in both women and men. • Osteoporosis can potentially be identified in patients with suspected wrist fractures. • DXR can potentially be used for selective osteoporosis screening.

The Effects of 8 Years of Continuous Denosumab Treatment on Bone Mineral Density and Biochemical Markers of Bone Turnover in a Phase 2 Study

s 481 Results: Hip fractures occurred in 68 (6%) participants. The median 10 year hip fracture risks were 4.1% for FRAX without BMD, 1.9% for FRAX with BMD, 5.6% for Garvan without BMD, and 3.9% for Garvan with BMD. The correlations of the predicted hip fracture risk of the two models were Pearson R 5 0.721 and Spearman rank R 5 0.890 for FRAX and Garvan without BMD, and Pearson R 5 0.754; Spearman rank R 5 0.913 for FRAX and Garvan with BMD (all P ! 0.01). The kappa scores were FRAX and Garvan without aBMD 0.649, and FRAX and Garvan with aBMD 0.699. Conclusions: These data show that there is good agreement between the two calculators for 10-year hip fracture risk. 004 Abstracts Invited for Oral Presentation THE EFFECTS OF 8 YEARS OF CONTINUOUS DENOSUMAB TREATMENT ON BONE MINERAL DENSITY AND BIOCHEMICAL MARKERS OF BONE TURNOVER IN