Total Hip T-score Research Articles

The relationship between sex steroids, bone turnover and vertebral fracture prevalence in asymptomatic men

To examine the association between oestradiol (E2), testosterone (T), SHBG levels and vertebral fractures' (VFs) prevalence in asymptomatic men. The study cohort consists of a population of 112 consecutive men (mean±SD (range) age, weight and BMI were 62.9±9.2 (41-84) years, 75.0±13.8 (45-120) kgs and 26.4±4.7 (18.0-39.6) kg/m(2), respectively). Lateral vertebral fracture assessment (VFA) images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative approach and morphometry. Serum levels of T, E2, CTx and osteocalcine were measured. Free androgen index (FAI) and free estradiol index (FEI) were calculated respectively from the ratio of serum T and E2 to SHBG. Among the 112 men, 38 (33.9%) had densitometric osteoporosis, and on VFA, VFs were identified in 60 (53.5%): 24 men had grade 1 and 36 had grade 2 or 3 VFs (32.1%). Men with VFs weighted less and had a statistically significant lower lumbar spine and total hip BMD and T-scores than those without a VFA-identified vertebral fracture. Levels of osteocalcine, CTx, and SHBG were statistically higher in men with grades 2 and 3 VFs than men with grade 1 VFs and those without VFs whereas FAI and FEI levels were significantly lower. Comparison of patients according to quartiles of SHBG levels showed that men in the highest quartile were older, had a lower lumbar spine and total hip BMD and a higher prevalence of osteoporosis and VFs. They had also higher levels of CTx. Stepwise regression analysis showed that the osteoporotic status and SHBG was independently associated to the presence of VFs. Men with asymptomatic densitometric VFs have lower BMD than subjects without VFs. They have evidence of higher SHBG levels and hence lower free sex steroids as well as increased bone resorption. This study confirms that BMD and CTx are the most important determinant of asymptomatic VFs, and that SHBG is an independent risk factor that must be taken into account.

Relationship between hip bone mineral density and lumbar disc degeneration: A study in elderly subjects using an eight‐level MRI‐based disc degeneration grading system

To study the relationship between hip bone mineral density (BMD), lumbar disc degeneration, and lumbar disc space narrowing in elderly subjects. The study cohort comprised 196 females and 163 males (age range, 67-89 years) with no age difference between the two groups. Anteroposterior total hip areal BMD was measured with DXA and lumbar spine MRI was acquired using a 1.5 Tesla scanner. Lumbar disc degeneration was assessed using an eight-level grading system wherein each grade represents a stepwise progression from normal disc to severe disc degeneration and disc space narrowing. After controlling for the age effect, no significant relationship was observed between total hip T-score status and severity of disc degeneration. There was no significant difference in total hip BMD in the subjects with or without the disc space narrowing (P < 0.05). Female subjects are more likely to have a narrowed disc space than males at all levels, and being statistically significant at L3/4 and L4/5 levels, and with an overall significance of P = 0.007. There was no association observed between hip BMD and lumbar disc degeneration. Elderly females were more likely to have a narrowed lumbar disc space than elderly males.

Potential Association of Posttraumatic Stress Disorder and Decreased Bone Mineral Density in Repatriated Prisoners of War

We conducted a retrospective evaluation of bone mineral density data collected during routine medical follow-up evaluations of 241 Vietnam-era male repatriated prisoners of war, with and without the lifetime diagnosis of posttraumatic stress disorder (PTSD), and 79 subjects in a comparison group. Dual-energy X-ray absorptiometry scans evaluated total hip and lumbar spine T-scores. A multivariate analysis of covariance was performed on the data using age, body mass index, ethnicity, and reported alcohol consumption as covariates. There was a significant effect of group on total hip, but not lumbar spine, T-scores. Pairwise comparisons revealed statistically lower total hip T-scores in repatriates with a lifetime history of PTSD in comparison to both the comparison group and repatriates without a lifetime history of PTSD. In this study of elderly repatriated prisoners of war, we noted an association between a lifelong history of PTSD and decreased bone mineral density at the hip.

Female patients with low systemic BMD

Sir—We read with interest the paper of Alm et al. (2009). The authors looked at post- total hip arhtroplasty periprosthetic (THA) bone changes in 39 subjects using DXA to analyse bone mineral density (BMD) in the Gruen zones surrounding the femoral prosthesis component. The purpose of the study was to look for factors such as bone mineral status that might influence femoral periprosthetic bone loss. In Figure 4 of their paper, the authors graphed the change in BMD in Gruen zone 7 at 2 years post-THA expressed as a percentage of baseline BMD at that site (y-axis) against the lowest preoperative T score from lumbar spine, proximal femur or non-dominant distal forearm (x-axis). From the significant positive correlation they obtained between these graphed variables, they concluded that”low preoperative systemic BMD was associated with higher bone loss in Gruen zone 7”. We would like to introduce a note of caution here because we will show that it is possible to demonstrate a significant correlation between the variables as defined by Alm et al when there is absolutely no influence of systemic BMD on postoperative BMD change at Gruen zone 7. In order to do this we need to mimic their experimental data with “mock data” for both x and y variables as per Alm's Figure 4. From inspection of that figure, the x-axis T-scores appear to have a mean of around -1.5 and a standard deviation (SD) of 1. From this information, it is possible to produce a set of 39 random numbers normally distributed with this mean and SD using, for example, the “Data Analysis” toolkit in Microsoft Excel. This gives us our x variable. The y variable is comprised of a numerator showing the BMD difference between Gruen zone 7 BMD at 2 years and that at a preoperative baseline. From Alm et al's data in Table 2, there is an average Gruen zone 7 BMD loss of -0.25 g/cm2 over 2 years. We make the assumption that this is fixed at that value for all patients, i.e. no possibility of variation with systemic bone mineral status. The denominator of the y variable is the baseline Gruen zone 7 BMD expressed in g/cm2. From our own data on 26 adult females scheduled for THA, we obtain a regression equation for the excellent positive correlation of baseline Gruen zone 7 BMD against baseline Total Hip T-score as expressed below: It is reasonable to accept this equation to an estimator for baseline Gruen zone 7 BMD given that Total Hip T-score is accepted as the most relevant indicator of systemic bone loss. Therefore, we have constructed mock data for both the numerator and denominator of the y variable and can therefore combine these to provide “mock data” for the y variable. We now have a y variable incorporating a constant BMD change in Gruen zone 7. If we proceed to look for a “relation” between these “mock” x and y variables, we find that there is a strong positive correlation with the following regression equation: From inspection of Alm et al's Figure 4, the y-intercept is approximately -14 and the gradient is approximately 5.4. Therefore, our mock data gives similar results to the experimental data of Alm et al. This occurs despite our choosing a constant BMD change in Gruen zone 7 at 2 years postoperatively, i.e. a change that was independent of systemic bone mineral status. The reason we get a “false”positive correlation with our data is that the y variable denominator and the x variable, both of which are preoperative assessments, are highly correlated, i.e. a low Total Hip T-score corresponds to a low Gruen Zone 7 baseline BMD and because this appears on the denominator of the y variable, it increases the apparent % bone loss represented by that variable. This analysis suggests that the conclusions made by Alm et al on the basis of their Figure 4 must be viewed with some caution. However, perhaps the most clinically important message from their study is that if you start with poor quality bone at the femoral prosthesis, any further postoperative loss whether related to systemic bone mineral status or not will not improve the situation.

The effect of PTH(1–84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial

We explored the effects of PTH(1-84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1-84) but not strontium ranelate, indicating a different mechanism of action between these agents. PTH(1-84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1-84) and SR on bone remodeling. A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (≥50 years of age, lumbar spine, or total hip T-score ≤-2.5 SD) to assess the effect of SR as compared to PTH(1-84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 μg PTH(1-84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D(3) and 1,000 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL). Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1-84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1-84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1-84) treatment. Safety profiles concur with previous analyses. PTH(1-84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1-84) in postmenopausal women with osteoporosis.

High prevalence of reduced bone mineral density in primary HIV-1-infected men

To assess the bone mineral density (BMD) in a cohort of men with primary HIV-1 infection (PHI). Thirty-three men with PHI had a dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck and total hip. Osteopenia and osteoporosis were defined according to WHO criteria as T-scores between -1 and -2.5 and -2.5 or less, respectively. The association between clinical and laboratory parameters and BMD was investigated using multivariable linear regression analysis. Mean age was 38 (SD 9) years and mean body mass index (BMI) 22.7 (SD 3.3) kg/m. Twenty-four men (73%) had a negative or indeterminate Western blot, 32 men (97%) were combination antiretroviral therapy-naive. Mean plasma HIV-1 RNA was 5.0 (SD 1.2) log10 copies/ml. Mean lumbar spine T (-0.8, SD 1.3, P = 0.001) and Z-scores (-0.7, SD 1.3, P = 0.004) and femoral neck T-score (-0.5, SD 0.9, P = 0.003) were significantly lower compared to the reference population. 15/33 men (45%) had osteopenia and 2/33 (6%) osteoporosis. Markers of bone turnover did not differ between patients with or without osteopenia/osteoporosis. Age was negatively associated with femoral neck (beta-coefficient = -0.05, P < 0.001) and total hip T-scores (beta = -0.03, P = 0.04). BMI was associated with lumbar spine (beta = 0.3), femoral neck (beta = 0.2) and total hip (beta = 0.2) T-scores (P < 0.001) and thyroid-stimulating hormone (TSH) with lumbar spine (beta = 0.5, P = 0.045) and femoral neck T-scores (beta = 0.4, P = 0.005). Increased plasma viral load was associated with lower total hip T-scores (beta = -0.2, P = 0.02). Reduced BMD was prevalent in PHI men and was associated with increased age, lower BMI and TSH levels, and higher levels of HIV-1 viremia.

Expected frequency of femoral neck fractures by fall in the osteoporotic and osteopenic East Slovak female population: Epidemiological study

To compare an expected frequency of pathological FSI values with an expected frequency of pathological BMD (T-score < or = -2.5 SD) in the total hip area in the East Slovak female population. We analyzed the data in the sample of 3,215 East Slovak women with a primary or secondary osteopenia and osteoporosis and with risk factors for osteoporosis, aged 20-89 years, x = 58.9 years, 95% CI (55.15; 60.35). Measured variables: T-score total hip left and FSI left (femur strength index with dual energy X-ray absorptiometry. In the East Slovak female population we can expect 6.25% of women with osteoporosis in the total hip area and 14.54% of women with FSI <1, i.e. these women will suffer a femoral neck fracture in case of a fall. The expected frequency of the incidence of pathological FSI values of the East Slovak female population is 2.33 times higher than the expected frequency of the incidence of pathological T-score for osteoporosis measured in the total hip area. The measurement of FSI variable values may discover a higher percentage of women with a risk of femoral neck fracture by fall than the measurement of BMD variable values in the total hip area. This disproportion shows that even a patient with osteopenia measured in the total hip area may sustain a femoral neck fracture by fall, when she has adverse values of geometric variables of proximal femur (biomechanically unfavourable proximal femur configuration).

Long-term prospective study of osteoporotic patients treated with percutaneous vertebroplasty after fragility fractures

This paper presents a prospective study on factors that could influence fracture risk after percutaneous vertebroplasty (PVP) in 115 osteoporotic patients. The mean follow-up was 39 months. The incidence of new fractures after PVP was 27.8%. Low body mass index (BMI), bone mineral density (BMD), and vitamin D are factors associated with increased risk of new fractures. The purpose of this study was to evaluate factors that could increase the occurrence of new vertebral fractures (VFx) after PVP. In our prospective study, we included patients of both sexes with osteoporosis (OP) and at least one painful VFx. We performed a baseline biochemical evaluation (including vitamin D plasma levels) and collected demographic, BMD, and clinical data. One hundred fifteen patients were treated with PVP and assigned to oral bisphosphonates plus Ca and vitamin D. The patients returned to control visits after 1, 3, and 6 months and every 6 months thereafter. X-rays film of the dorsolumbar spine was repeated every 12 months, or in case of pain that would suggest VFx occurrence. The mean follow-up was 39 ± 16 months (range, 15-79). Thirty-two patients (27.8%) had new fragility VFx, all symptomatic. All the fractured patients agreed to undergo a new PVP. We compared the patients who had new VFx to those who had not, and we found significantly lower BMI, total hip, and femoral neck T-scores in the group with new VFx. Furthermore, baseline plasma levels of 25(OH) vitamin D (25(OH)D) were significantly lower in this group. Upon analyzing plasma levels of 25(OH)D 12 months after PVP, we found that a significant difference still persisted: 22 ± 12 (group with new VFx) vs. 41 ± 22 ng/ml (group with no VFx; p < 0.01). We found that in patients with OP treated with PVP, the incidence of new VFx was 27.8% after 39 months; low BMI, BMD, and vitamin D are factors associated with increased risk of new VFx in patients treated with PVP.

Cost effectiveness of teriparatide and PTH(1-84) in the treatment of postmenopausal osteoporosis

Objectives:The purpose was to assess the cost effectiveness from a societal perspective of the recombinant human parathyroid hormones: PTH(1-34) (teriparatide) and PTH(1-84) for patients with osteoporosis with similar characteristics to patients treated in normal clinical practice in Sweden.Methods:A Markov model of osteoporosis in postmenopausal women was developed using 6-month cycles and a lifetime horizon. The model was populated with patients similar to the Swedish cohort of the European Forsteo Observational Study (postmenopausal women; mean age: 70 years, total hip T-score: −2.7 and 3.3 previous fractures). The cost effectiveness of both teriparatide and PTH(1-84) was estimated compared to no treatment and each other. Relative effectiveness assumptions were based on efficacy estimates from two phase III clinical trials.Results:The cost per QALY gained of teriparatide vs. no treatment was estimated at €43,473 and PTH(1-84) was estimated at €104,396. Teriparatide was indicated to be less costly and associated with more life-years and QALYs than PTH(1-84). When assuming no treatment effect on hip fractures the cost per QALY gained was €88,379. In the sensitivity analysis the cost effectiveness did not alter substantially with changes in the majority of the model parameters except for the residual effect of the treatment after stopping therapy.Conclusions:Based on the efficacy estimates from pivotal clinical trials and characteristics of patients treated in clinical practice in Sweden, teriparatide seems to be a more cost-effective option than PTH(1-84) when compared to no treatment. The relative efficacy between the two PTH compounds was based on an indirect comparison from two separate clinical trials which has to be considered when interpreting the results.

Accuracy of quantitative ultrasound parameters in the diagnosis of osteoporosis

Abstract Quantitative ultrasound (QUS) is of increasing interest for evaluation of osteoporosis because, compared with dual-energy X-ray absorptiometry (DXA), it is portable, less expensive, and radiation-free. The aim of our study was to determine the sensitivity, specificity, and cut-off values of quantitative ultrasound parameters in identifying patients with osteoporosis compared to the World Health Organization (WHO) standard definition. We performed a cross-sectional investigational study of 73 subjects, and determined total hip and lumbar spine T-scores by dual-energy X-ray absorptiometry (DXA) (Prodigy Advance Lunar-GE). The QUS parameters (broadband ultrasound attenuation [BUA], speed of sound, bone mineral density, the stiffness index, and QUS T-score) were determined with Sahara Hologic equipment. The AUC was 0.81 (95% CI 0.67–0.95, p&lt;0.05) for speed of sound (SOS) and 0.76 (95% CI 0.62–0.90, p&lt;0.05) for BUA for the patients with DXA T-scores ≥ −1 DS; the cut-off values were 1542.2 meters per second for SOS and 63.3 dB/MHz for BUA. In patients with DXA T-scores ≤ − 2.5 DS, AUC was 0.80 (95% CI 0.70–0.90, p&lt;0.05) for SOS, and 0.76 (95% CI 0.65–0.87, p&lt;0.05) for BUA. The cut-off values were 1504.95 meters per second for SOS and 49.5 dB/MHz for BUA. Pearson correlation coefficients were positive and statistically significant (&gt; 50%) for all QUS parameters in both groups, (2-tailed, p&lt;0.05). QUS parameters correctly identified normal patients (false negative 34.21% and false positive 2.53%) and those with osteoporosis (false negative 8.55% and false positive 7.82%). The patients with QUS parameters between the cut-off values corresponding to DXA T-scores of −1 SD and − 2.5 SD should be further evaluated by DXA.

Logistic regression in estimates of femoral neck fracture by fall

The latest methods in estimating the probability (absolute risk) of osteoporotic fractures include several logistic regression models, based on qualitative risk factors plus bone mineral density (BMD), and the probability estimate of fracture in the future. The Slovak logistic regression model, in contrast to other models, is created from quantitative variables of the proximal femur (in International System of Units) and estimates the probability of fracture by fall. The first objective of this study was to order selected independent variables according to the intensity of their influence (statistical significance) upon the occurrence of values of the dependent variable: femur strength index (FSI). The second objective was to determine, using logistic regression, whether the odds of FSI acquiring a pathological value (femoral neck fracture by fall) increased or declined if the value of the variables (T-score total hip, BMI, alpha angle, theta angle and HAL) were raised by one unit. Bone densitometer measurements using dual energy X-ray absorptiometry (DXA), (Prodigy, Primo, GE, USA) of the left proximal femur were obtained from 3 216 East Slovak women with primary or secondary osteoporosis or osteopenia, aged 20-89 years (mean age 58.9; 95% CI: -58.42; 59.38). The following variables were measured: FSI, T-score total hip BMD, body mass index (BMI), as were the geometrical variables of proximal femur alpha angle (α angle), theta angle (θ angle), and hip axis length (HAL). Logistic regression was used to measure the influence of the independent variables (T-score total hip, alpha angle, theta angle, HAL, BMI) upon the dependent variable (FSI). The order of independent variables according to the intensity of their influence (greatest to least) upon the occurrence of values of the dependent FSI variable was found to be: BMI, theta angle, T-score total hip, alpha angle, and HAL. An increase of one unit of an independent variable was shown, with statistical significance, to either raise or decrease the odds of the dependent FSI variable. Specific findings were as follows: an increase by 1° of the α angle escalated the probability of FSI acquiring a pathological value by 1111 times; an increase by 1° of the θ angle was found to boost these odds 1231 times; an increase by 1 mm of the HAL was found to increase these odds by 1043 times; an increase by 1.0 kg/m(2) of the BMI raised the odds 1302 times; an increase by +1 standard deviation of the value of the T-score total hip subsequently decreased these odds 198 times. The equation of the Slovak regression model makes it possible in praxis to determine the probability or absolute risk of femoral neck fracture by fall at those densitometrical workplaces without a program for measuring the FSI variable.

Prevalence and risk factors of vertebral fractures in women with rheumatoid arthritis using vertebral fracture assessment

To study the prevalence and risk factors of vertebral fractures (VFs) in a large cohort of patients with RA using VF assessment (VFA). We enrolled 172 women with RA, none of whom were taking osteoporosis medications. Patients underwent dual X-ray absorptiometry at the hip and spine and VFA, and completed a questionnaire. Radiological status was assessed by the modified Sharp erosion and narrowing score. VFA was classified using a combination of Genant semi-quantitative approach and morphometry. Patients had a mean (s.d.) disease duration of 8.4 (5.2) years. VFs were detected in 36% (62/172). This group of women had a statistically significant lower weight, height and lumbar spine and total hip BMD and T-scores than those without a VFA-identified VF. They also had more long-standing and severe disease and a greater consumption of corticosteroids. Stepwise regression analysis showed that the presence of VFs was independently associated with low weight and total hip T-score and long disease duration, CRP and Sharp erosion score. RA is a risk factor on its own for the development of osteoporosis and VFs and this risk increases more with low weight, disease duration and severe course of disease. These findings may suggest that to prevent the development of VFs, precautions should be taken immediately to suppress the disease activity and correct the weight loss in patients with RA.

Bone-specific alkaline phosphatase (BSAP) and serum N-telopeptide (sNTX) as predictors of bone loss in postmenopausal women with early breast cancer receiving letrozole as adjuvant therapy: a 5-year study (Z-FAST).

Abstract Abstract #2067 Background: Changes in biochemical markers of bone turnover are expected to be predictors of long-term changes in bone mineral density (BMD). We studied the potential of bone-specific alkaline phosphatase (BSAP) and serum N-telopeptide (sNTX) at 6 and 12 months (mo) in predicting BMD of the lumber spine (LS) and total hip (TH) at 48 mo in Z-FAST study.&amp;#x2028; Methods: Postmenopausal women with ER+ and/or PR+ early stage breast cancer were randomized 1:1 into Up-front (U) or Delayed (D) arms (N=301 in each). Patients (pts) in U received zoledronic acid (ZOL) 4 mg IV q6 mo starting at baseline; pts in D started ZOL q6 mo when their LS or TH T-score fell below -2. All pts started Letrozole 2.5 mg/day for 5 years. Levels of BSAP and sNTX were assessed at screening and every 6 mo on a subset of pts. LS and TH BMD were assessed by dual-energy x-ray absorptiometry (DEXA) at screening, 6 mo and every 12 mo thereafter for all available pts. This is an exploratory analysis to investigate the correlation between short-term % changes from baseline in BSAP and sNTX and long-term % changes from baseline in BMD. Pearson correlations and Receiver Operating Characteristics (ROC) analysis were performed. We report the results based on 48 mo data.&amp;#x2028; Results: The Pearson correlations between % change in BSAP at 6 mo and LS BMD at 48 mo were -0.13 [(N=38, not significant (NS)] and -0.17 (N=39, NS) in arms U and D respectively. The correlations between % change in BSAP at 12 mo and LS BMD at 48 mo were -0.15 (N=39, NS) in U and -0.43 (N=38, p=0.0077) in D. Very similar correlations were obtained for % change in sNTX at 6, 12 mo and LS BMD at 48 mo in D, but in U the correlations were smaller and positive. The correlations between % change of both markers at 6, 12 mo and TH BMD at 48 mo were all NS at 0.05. ROC analysis showed that at best performance (maximum of sensitivity plus specificity), for any increase in sNTX at 12 mo, the sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) to predict LS BMD loss at 48 mo was 74%, 77%, 85% and 63% in D. For BSAP change of 3%, the four ROC parameters were 71%, 71%, 81% and 59% respectively. For prediction of TH BMD loss, the SE, SP and NPV were lower for both markers with higher PPV. In U, the SE, SP and PPV were all much lower with very high NPV for both markers and BMD loss.&amp;#x2028; Conclusion: Interim results of Z-FAST data show that short-term changes in BSAP and sNTX have the potential for predicting long-term bone loss. The weaker correlations in U also suggest that zoledronic acid may have a direct preventive effect on bone loss independent of changes in the markers. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2067.

Assessment of determinants for osteoporosis in elderly men

The aim of this cross-sectional study was to determine and quantify some determinants associated to low bone mineral density (BMD) in elderly men. This study showed that ageing, a lower body mass index (BMI), a higher blood level of C-terminal cross-linking telopeptides of type I collagen (CTX-1), family history of osteoporosis, and/or fracture and prior fracture were associated with bone mineral density. Our aims were to identify some determinants associated to low bone mineral density in men and to develop a simple algorithm to predict osteoporosis. A sample of 1,004 men aged 60 years and older was recruited. Biometrical, serological, clinical, and lifestyle determinants were collected. Univariate, multivariate, and logistic regression analyses were performed. Receiver operating characteristic analysis was used to assess the discriminant performance of the algorithm. In the multiple regression analysis, only age, BMI, CTX-1, and family history of osteoporosis and/or fracture were able to predict the femoral neck T-score. When running the procedure with the total hip T-score, prior fracture also appeared to be significant. With the lumbar spine T-score, only age, BMI, and CTX-1 were retained. The best algorithm was based on age, BMI, family history, and CTX-1. A cut-off point of 0.25 yielded a sensibility of 78%, a specificity of 59% with an area under the curve of 0.73 in the development and validation cohorts. Ageing, a lower BMI, higher CTX-1, family history, and prior fracture were associated with T-score. Our algorithm is a simple approach to identify men at risk for osteoporosis.

Effective inhibition of aromatase inhibitor‐associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole

Letrozole is safe and effective in postmenopausal women with estrogen receptor-positive early breast cancer, but long-term aromatase inhibitor use may cause bone loss and increase fracture risk. This study evaluated an immediate or delayed strategy of bone protection therapy with zoledronic acid. A total of 1065 patients who were receiving adjuvant letrozole were randomized to immediate-start or delayed-start zoledronic acid (4 mg intravenously biannually for 5 years). The delayed group received zoledronic acid if lumbar spine or total hip T-score decreased below -2.0 or when a nontraumatic fracture occurred. The primary endpoint was change in lumbar spine bone mineral density (BMD) at Month 12. Secondary endpoints included changes in total hip BMD, serum bone turnover markers, and safety at Month 12. Lumbar spine BMD increased from baseline in the immediate arm, while it decreased from baseline in delayed-arm patients. At Month 12, the differences between the groups in lumbar spine and total hip BMD were 5.7% (P < .0001; 95% confidence intervals [CI], 5.2% to 6.1%), and 3.6% (P < .0001; 95% CI, 3.3 to 4.0%), respectively. Both regimens were well tolerated with few serious adverse events. Bone pain was higher in the immediate group, as expected, because some patients experienced acute-phase reactions after zoledronic acid infusion. At 12 months, immediate zoledronic acid therapy prevented bone loss in postmenopausal women who were receiving adjuvant letrozole.

Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study

Objective : To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance. Design : Randomized clinical trial. Setting : University hospital physiotherapy department. Subjects : Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score (SD) of —1.8 (0.8). Interventions : A three-month programme consisting of exercise/protein including training of muscular strength, co-ordination, balance and endurance. Calcium/ vitamin D was supplemented in all participants for a 12-month period. Outcome measures : Assessment took place prior to and following the months 3, 6, 9 and at the end of the study; primary dependent variables assessed were risk of falling (Berg Balance Test) and postural balance (forceplate). Secondary measures included body composition, strength, activity level, number of falls, bone mineral content, biochemical indices, nutritional status and general health. Results : Significant reductions of risk of falling (repeated measures ANOVA F = 8.90, P = 0.008), an increase in muscular strength (ANOVA F = 3.0, P = 0.03), and an increase in activity level (ANOVA F = 3.38, P = 0.02) were found in the experimental group as compared to the control group. Further on, there was 89% reduction of falls reported in the experimental group (experimental pre/post 8/1 falls; control group pre/post 5/6 falls). Conclusion : This study provides support for our intervention programme aimed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis. The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger randomized trial.

Diagnostic Agreement at the Total Hip Using Different DXA Systems and the NHANES III Database

In 1997, the National Health and Nutrition Examination Survey III (NHANES III) total hip reference database was adopted for T-score derivation in an effort to optimize diagnostic agreement among densitometers from different manufacturers. Our study was undertaken to evaluate the effectiveness of the NHANES III standardized database at achieving agreement in diagnostic classification (normal, osteopenia, or osteoporosis) based on total hip T-scores comparing 2 different dual-energy X-ray absorptiometry (DXA) systems. This was a retrospective analysis of standard bilateral hip and lumbar spine scans done in duplicate for 60 women scanned on both a GE Lunar Prodigy and Hologic Delphi DXA system. Classification based on lumbar spine T-scores using manufacturer-specific databases was also compared as no standardized lumbar spine reference database exists. Subject's mean age was 62 yr (range: 47–83 yr). There was no statistically significant difference in diagnostic classification between DXA systems (Prodigy vs Delphi), with agreement (same women classified same way) of 92% at the left total hip. Agreement was 100% when T-scores were greater than or equal to −0.8 and less than or equal to −1.2. There was 90% agreement between DXA systems at the lumbar spine. For both hip and spine, all diagnostic discrepancies occurred when the T-scores were at or near transition thresholds between normal and osteopenia or osteopenia and osteoporosis. The difference in mean T-scores between DXA systems at left total hip was 0.11 vs 0.32 for lumbar spine ( p less than 0.001). Use of the NHANES III standardized database results in good diagnostic agreement at total hip between Prodigy and Delphi.

Preservation of neuroendocrine control of reproductive function despite severe undernutrition.

Anorexia nervosa (AN) is characterized by low weight and self-imposed caloric restriction and leads to severe bone loss. Although amenorrhea due to acquired GnRH deficiency is nearly universal in AN, a subset of patients maintains menses despite low weight. The mechanisms underlying continued GnRH secretion despite low weight in these patients and the impact of gonadal hormone secretion on bone mineral density (BMD) in such eumenorrheic, low-weight patients remain unknown. We hypothesized that 1) eumenorrheic women with AN would have higher body fat and levels of nutritionally dependent hormones, including leptin and IGF-I, than amenorrheic women with AN and comparable body mass index; and 2) BMD would be higher in these women. We also investigated whether the severity of eating disorder symptomatology differed between the groups. We studied 116 women: 1) 42 low-weight women who fulfilled all Diagnostic and Statistical Manual of Mental Disorders (fourth edition) diagnostic criteria for AN, except for amenorrhea; and 2) 74 women with AN and amenorrhea for at least 3 months. The two groups were similar in body mass index (17.1 +/- 0.2 vs. 16.8 +/- 0.2 kg/m(2)), percent ideal body weight (78.2 +/- 0.8% vs. 76.7 +/- 0.8%), duration of eating disorder (70 +/- 13 vs. 59 +/- 9 months), age of menarche (13.2 +/- 0.3 vs. 13.5 +/- 0.2 yr), and exercise (4.5 +/- 1.0 vs. 4.2 +/- 0.5 h/wk). As expected, eumenorrheic patients had a higher mean estradiol level (186.6 +/- 19.0 vs. 59.4 +/- 2.5 nmol/liter; P < 0.0001) than amenorrheic subjects. Mean percent body fat, total body fat mass, and truncal fat were higher in eumenorrheic than amenorrheic patients [20.9 +/- 0.9% vs. 16.7 +/- 0.6% (P = 0.0001); 9.8 +/- 0.5 vs. 7.8 +/- 0.3 kg (P = 0.0009); 3.4 +/- 0.2 vs. 2.7 +/- 0.1 kg (P = 0.006)]. The mean leptin level was higher in the eumenorrheic compared with the amenorrheic group (3.7 +/- 0.3 vs. 2.8 +/- 0.2 ng/ml; P = 0.04). Serum IGF-I levels were also higher in the eumenorrheic than in the amenorrheic group (41.8 +/- 3.7 vs. 30.8 +/- 2.3 nmol/liter; P = 0.02). There were only minor differences in severity of eating disorder symptomatology, as measured by the Eating Disorders Inventory, and where differences were observed, eumenorrheic subjects manifested more severe symptomatology than amenorrheic subjects. Mean BMD at the posterior-anterior and lateral spine were low in both groups, but were higher in patients with eumenorrhea than in those with amenorrhea [posterior-anterior spine T-score, -0.9 +/- 0.1 vs. -1.9 +/- 0.1 (P < 0.0001); lateral spine T-score, -1.2 +/- 0.1 vs. -2.3 +/- 0.2 (P < 0.0001)]. In contrast, preservation of menstrual function was not protective at the total hip (total hip T-score, -0.9 +/- 0.1 vs. -1.1 +/- 0.1; P = 0.27), trochanter, or femoral neck. In summary, patients with eumenorrhea had more body fat and higher serum leptin levels than their amenorrheic counterparts of similar weight. Moreover, reduced bone density was observed in both groups, but was less severe at the spine, but not the hip, in women with undernutrition and preserved menstrual function than in amenorrheic women of similar weight. Therefore, fat mass may be important for preservation of normal menstrual function in severely undernourished women, and this may be in part mediated through leptin secretion. In addition, nutritional intake and normal hormonal function may be independent contributors to maintenance of trabecular bone mass in low-weight women.

Osteoporosis in Pulmonary Clinic Patients : Does Point-of-Care Screening Predict Central Dual-Energy X-ray Absorptiometry?

Patients in a pulmonary clinic have disorders that predispose them to osteoporosis and may use glucocorticoid therapy, which has been associated with low bone mineral density (BMD) and increased fracture risk. Ideally, all patients at risk for osteoporosis would be screened using the best test available, which is central BMD by dual-energy x-ray absorptiometry (DXA). We proposed to stratify the risk for osteoporosis by the use of a simple questionnaire and point-of-care heel ultrasound BMD measurements. Cross-sectional screening study. Pulmonary clinic in a single Veterans Affairs Medical Center. Approximately 200 male and female patients who had not had previous BMD testing were eligible for the study, and 107 gave consent. One hundred seven men (white, 71 men; black, 35 men; and Asian, 1 man) underwent heel BMD testing and filled out a questionnaire. Ninety-eight men underwent a central DXA. Of 98 subjects, 24.5% had a spine, total hip, or femoral neck (FN) T-score of <or= -2.5, which is the generally accepted definition of osteoporosis diagnosed using DXA, and 44.9% had a T-score of <or= -2.0. The best-fit models for predicting FN or total hip BMD included body weight, heel BMD, corticosteroid use for >or= 7 days, and race, which accounted for 52 to 57% of the variance. When a heel ultrasound T-score of -1.0 was tested to predict a central DXA T-score of -2.0, the sensitivity was 61% and the specificity 64%. Adding the questionnaire score and body mass index (BMI) to the heel T-score improved sensitivity but not specificity. Moreover, BMI and age predicted central BMD with similar sensitivity and specificity. Importantly, of 24 patients with a central DXA T-score of <or= -2.5, only 14 were identified by a heel T-score of <or= -1.0. Although the findings from a heel ultrasound plus the answers to a questionnaire were reasonably good indicators for predicting the presence of low BMD, little predictability was gained over the use of BMI and age. In a group of pulmonary clinic patients, the prevalence of osteoporosis was clinically significant, and central DXA testing was the preferable technique for identifying patients who were at risk for fracture.

Does follow-up of osteoporotic women treated with antiresorptive therapies improve effectiveness?

The use of biochemical markers of bone turnover has been advocated to improve follow-up of women receiving antiresorptive therapies for osteoporosis, but this strategy is not yet supported by trials showing it improves effectiveness of treatments. To explore the potential value of markers of bone turnover to monitor antiresorptive treatments of osteoporosis, we conducted a decision analysis using a decision tree and Markov modeling. We have compared two strategies: treatment of a woman without specific monitoring; and treatment of this woman with measurement of a serum marker of bone resorption after 3 months of treatment, with change of treatment if response to treatment assessed by this marker was not satisfactory. The base case is the treatment of a 60-year-old osteoporotic woman with a total hip T-score of -3, using a second generation bisphosphonate during 5 years. We found that follow-up produced slightly greater quality adjusted life years (QALYs) than no follow-up (8.1560 vs 8.1532, i.e. a one day difference). In a two-way sensitivity analysis, the follow-up option produced higher QALYs so long as adherence rate with follow-up was equal or superior to the proportion of women who adhered without follow-up. For example, if the proportion of women adherent to treatment was increased from 50% to 60% by follow-up, then the expected value of the follow-up branch was increased from 8.1560 QALYs to 8.1800 QALYs (i.e. a difference of 9 days). In addition, the higher the non-response rate, the greater the benefit from monitoring with a biochemical marker. In conclusion, our decision analysis model suggests that follow-up of osteoporotic women treated with a second generation bisphosphonate during a 5-year period using an early measurement of a serum marker of bone resorption may increase effectiveness of the treatment on quality of life, but the effect is very small. So, the use of follow-up measures of bone turnover may be based on patient and physician preferences.