Bone architecture, bone material properties, and bone turnover in non-osteoporotic post-menopausal women with fragility fracture.

Macro- and microarchitectural, bone material property, dynamic histomorphometric, and bone turnover marker data were studied in normal bone mineral density (BMD) post-menopausal women with fragility fracture. Women with fracture had thinner iliac cortices and more homogeneous bone material properties in cortical bone than age/BMD-matched non-fracture women. Low cortical thickness and bone tissue heterogeneity in normal BMD women are associated with prevalent fragility fracture. INTRODUCTION: Bone mass (bone mineral density, (BMD)) of the spine and hip is today's best single measurement for evaluating future fragility fracture risk. However, the majority of fragility fractures occur in women with BMD T-score above the WHO osteoporotic BMD threshold of - 2.5, indicating that non-BMD endpoints may play a role in their fragility fractures. We hypothesize that in non-osteoporotic women, bone micoarchitecture, bone material properties, dynamic histomorphometric endpoints, and bone turnover markers are related to fragility fracture. METHODS: Two groups (N = 60 each) of post-menopausal women with total hip BMD T-score ranging from + 0.3 to -2.49 were recruited: fragility fracture and age/BMD-matched, non-fragility fracture women. Normal (T-score > - 0.99) and osteopenic (T-score ≤ - 1.0) BMD cohorts were designated within both the fracture and non-fracture groups. Transiliac biopsy specimens were obtained to evaluate dynamic histomorphometric and microarchitectural endpoints and bone material properties by static and dynamic nanoindentation testing. All variables for fracture and non-fracture women within each BMD cohort were compared by the Wilcoxon signed-rank test (P < 0.01). RESULTS: Compared to non-fracture/normal BMD women, fracture/normal BMD women display lower iliac cortical thickness (- 12%, P = 0.0041) and lower heterogeneity of hardness (- 27%, P = 0.0068), elastic modulus (- 35%, P = 0.0009), and storage modulus (- 23%, P = 0.0054) in the cortical bone tissue, and lower heterogeneity of hardness (- 13%, P = 0.0088) in the trabecular bone tissue. Osteopenic women had no abnormalities related to fracture status. CONCLUSION: Post-menopausal women with normal BMD and fragility fracture have low cortical thickness and heterogeneity of several bone material properties in cortical and trabecular mineralized bone tissue. These differences may explain a portion of the excess bone fragility in women with normal BMD and fragility fracture.

In premenopausal women with idiopathic osteoporosis, lower bone formation rate is associated with higher body fat and higher IGF-1.

We examined serum IGF-1 in premenopausal IOP, finding relationships that were opposite to those expected: higher IGF-1 was associated with lower bone formation and higher body fat, and lower BMD response to teriparatide. These paradoxical relationships between serum IGF-1, bone, and fat may contribute to the mechanism of idiopathic osteoporosis in premenopausal women. INTRODUCTION: Premenopausal women with idiopathic osteoporosis (IOP) have marked deficits in bone microarchitecture but variable bone remodeling. We previously reported that those with low tissue-level bone formation rate (BFR) are less responsive to teriparatide and have higher serum IGF-1, a hormone anabolic for osteoblasts and other tissues. The IGF-1 data were unexpected because IGF-1 is low in other forms of low turnover osteoporosis-leading us to hypothesize that IGF-1 relationships are paradoxical in IOP. This study aimed to determine whether IOP women with low BFR have higher IGF-1 and paradoxical IGF-1 relationships in skeletal and non-skeletal tissues, and whether IGF-1 and the related measures predict teriparatide response. METHODS: This research is an ancillary study to a 24 month clinical trial of teriparatide for IOP. Baseline assessments were related to trial outcomes: BMD, bone remodeling. SUBJECTS:  Premenopausal women with IOP(n = 34); bone remodeling status was defined by baseline cancellous BFR/BS on bone biopsy. MEASURES:  Serum IGF-1 parameters, compartmental adiposity (DXA, CT, MRI), serum hormones, and cardiovascular-risk-markers related to fat distribution. RESULTS: As seen in other populations, lower BFR was associated with higher body fat and poorer teriparatide response. However, in contrast to observations in other populations, low BFR, higher body fat, and poorer teriparatide response were all related to higher IGF-1: IGF-1 Z-score was inversely related to BFR at all bone surfaces (r = - 0.39 to - 0.46; p < 0.05), directly related to central fat (p = 0.05) and leptin (p = 0.03). IGF-1 inversely related to 24 month hip BMD %change (r = - 0.46; p = 0.01). CONCLUSIONS: Paradoxical IGF-1 relationships suggest that abnormal or atypical regulation of bone and fat may contribute to osteoporosis mechanisms in premenopausal IOP.

Bone remodeling and bone matrix quality before and after menopause in healthy women.

Acceleration of remodeling activity after menopause leads to bone loss and fragility, however, whether this is associated with modifications of bone matrix quality has been less studied. The impact of variation in bone remodeling rate on bone matrix has been studied mainly in pathologies or anti-osteoporotic treatments. However, in healthy women this has been less studied. We analyzed, at the global level, bone matrix quality in bone biopsies from 3 groups of healthy women (20 per group): 1) before menopause (PreM), 2) 1 year after menopause (PostM, paired biopsies with preM), and 3) 14 (±9) years after menopause (LT-PostM). The mean degree of mineralization (DMB) and heterogeneity index (HI) of mineralization were assessed by X-ray microradiography on whole bone matrix; intrinsic properties (mineral/organic ratio, mineral maturity, mineral crystallinity, collagen maturity) were assessed by Fourier Transform Infrared microspectroscopy, microhardness by microindentation, both at a global level and calculated by mean of several measurements over the whole tissue area. In PostM compared to PreM (bone remodeling rate had doubled), mean DMB measured on the entire bone plane (whole bone matrix) of the sample was not different. HI was increased in trabecular bone indicating a higher heterogeneity of mineralization. However, in PostM, mineral/organic ratio (trabecular) and microhardness (cortical and trabecular) were decreased, whereas mineral/collagen maturation or crystal size/perfection were unchanged. Thus, in PostM, the local mineral content and microhardness were first affected. In LT-PostM (bone remodeling rate was 3 times higher), the mean DMB was still not different. However, the mineral/organic ratio, microhardness, mineral maturity, crystallinity all were lower compared to PreM and PostM, in both cortical and trabecular bone. Bone remodeling rate was negatively correlated with microhardness, DMB, mineral/organic and crystallinity. This suggests that increases in bone remodeling rates after menopause have a direct impact on bone quality by inducing the formation of more extensive "immature" bone areas, but the amount of immature bone does not cause modification of the global DMB.

Effect of Macroanatomic Bone Type and Estrogen Loss on Osteocyte Lacunar Properties in Healthy Adult Women.

This is the first study to examine clinical human bone specimens by three-dimensional imaging to characterize osteocyte lacunar properties as a function of macroanatomic bone type and estrogen loss. We applied laboratory-based instrumentation [3D X-ray microscope (3DXRM), MicroXCT-200; Carl Zeiss/Xradia, Inc.] that reaches the same resolution as synchrotron microscopy. We used serial transiliac bone biopsy specimens to examine the effect of macroanatomic bone type and estrogen status on osteocyte lacunar properties. These properties include lacunar size (volume, axes lengths of the ellipsoidal lacunar voids), distribution (density, average near-neighbor lacunar distance), and shape factors (sphericity ratio, average eigenvalues, degree of equancy, elongation, and flatness) in both cortical and trabecular bone tissue. The lacunar properties (volume, surface area, density, near-neighbor distance, etc.) and the shape factors (E1, L1, L2, degree of equancy, degree of elongation) were different between cortical and trabecular bone regardless of estrogen status. In cortical bone and trabecular nodes, the lacunar void volume and surface area were either smaller or tended to be smaller in postmenopausal as compared to premenopausal women. The void volume-to-bone volume ratio of cortical bone showed declining trends with estrogen loss. While there were differences between trabecular and cortical bone tissue, the lacunar void sphericity ratio for trabecular struts shows decreasing trends in postmenopausal women. These data suggest that using 3DXRM can provide new insight into osteocyte lacunar properties in transiliac bone biopsies from patients with various skeletal disease/conditions and pharmaceutical treatments.

Intrinsic material property differences in bone tissue from patients suffering low-trauma osteoporotic fractures, compared to matched non-fracturing women.

Osteoporotic (low-trauma) fractures are a significant public health problem. Over 50% of women over 50yrs. of age will suffer an osteoporotic fracture in their remaining lifetimes. While current therapies reduce skeletal fracture risk by maintaining or increasing bone density, additional information is needed that includes the intrinsic material strength properties of bone tissue to help develop better treatments, since measurements of bone density account for no more than ~50% of fracture risk. The hypothesis tested here is that postmenopausal women who have sustained osteoporotic fractures have reduced bone quality, as indicated with measures of intrinsic material properties compared to those who have not fractured. Transiliac biopsies (N=120) were collected from fracturing (N=60, Cases) and non-fracturing postmenopausal women (N=60, age- and BMD-matched Controls) to measure intrinsic material properties using the nano-indentation technique. Each biopsy specimen was embedded in epoxy resin and then ground, polished and used for the nano-indentation testing. After calibration, multiple indentations were made using quasi-static (hardness, modulus) and dynamic (storage and loss moduli) testing protocols. Multiple indentations allowed the median and variance to be computed for each type of measurement for each specimen. Cases were found to have significantly lower median values for cortical hardness and indentation modulus. In addition, cases showed significantly less within-specimen variability in cortical modulus, cortical hardness, cortical storage modulus and trabecular hardness, and more within-specimen variability in trabecular loss modulus. Multivariate modeling indicated the presence of significant independent mechanical effects of cortical loss modulus, along with variability of cortical storage modulus, cortical loss modulus, and trabecular hardness. These results suggest mechanical heterogeneity of bone tissue may contribute to fracture resistance. Although the magnitudes of differences in the intrinsic properties were not overwhelming, this is the first comprehensive study to investigate, and compare the intrinsic properties of bone tissue in fracturing and non-fracturing postmenopausal women.

The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations.

Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence-based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one's genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach.

Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.

UNLABELLED: The aim was to meta-analyze randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention. Meta-analysis showed a significant 15 % reduced risk of total fractures (summary relative risk estimate [SRRE], 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). INTRODUCTION: Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults. METHODS: A PubMed literature search was conducted for the period from July 1, 2011 through July 31, 2015. RCTs reporting the effect of calcium plus vitamin D supplementation on fracture incidence were selected from English-language studies. Qualitative and quantitative information was extracted; random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for total and hip fractures. Statistical heterogeneity was assessed using Cochran's Q test and the I (2) statistic, and potential for publication bias was assessed. RESULTS: Of the citations retrieved, eight studies including 30,970 participants met criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures (SRRE, 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. A limitation is that this study utilized data from subgroup analysis of the Women's Health Initiative. CONCLUSIONS: This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.

Marrow adiposity assessed on transiliac crest biopsy samples correlates with noninvasive measurement of marrow adiposity by proton magnetic resonance spectroscopy ((1)H-MRS) at the spine but not the femur.

UNLABELLED: Measurement of marrow fat (MF) is important to the study of bone fragility. We measured MF on iliac biopsies and by spine/hip magnetic resonance spectroscopy in the same subjects. Noninvasively assessed spine MF and histomorphometrically assessed MF correlated well. MF quantity and relationships with bone volume differed by measurement site. INTRODUCTION: Excess marrow fat has been implicated in the pathogenesis of osteoporosis in several populations. In the bone marrow, adipocytes and osteoblasts share a common precursor and are reciprocally regulated. In addition, adipocytes may secrete toxic fatty acids and adipokines that adversely affect osteoblasts. Measurement of marrow fat is important to the study of mechanisms of bone fragility. Marrow fat can be quantified on bone biopsy samples by histomorphometry and noninvasively by proton magnetic resonance spectroscopy ((1)H-MRS). In this study, we evaluate relationships between marrow fat assessed using both methods in the same subjects for the first time. METHODS: Sixteen premenopausal women, nine with idiopathic osteoporosis and seven normal controls, had marrow fat measured at the iliac crest by bone biopsy and at the lumbar spine (L3) and proximal femur by (1)H-MRS. RESULTS: At L3, fat fraction by (1)H-MRS correlated directly and significantly with marrow fat variables on iliac crest biopsies (r = 0.5-0.8). In contrast, there were no significant correlations between fat fraction at the femur and marrow fat on biopsies. Marrow fat quantity (%) was greater at the femur than at L3 and the iliac crest and correlated inversely with total hip and femoral neck BMD by DXA. CONCLUSIONS: In summary, measurement of marrow fat in transiliac crest biopsies correlates with marrow fat at the spine but not the proximal femur by (1)H-MRS. There were site-specific differences in marrow fat quantity and in the relationships between marrow fat and bone volume.

Anthropometric models of bone mineral content and areal bone mineral density based on the bone mineral density in childhood study.

UNLABELLED: New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. INTRODUCTION: Previous descriptions of children's bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. METHODS: We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's bone mineral values. By balancing high adjusted R(2) values with clinical needs, two models are examined. RESULTS: At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below -2, from the standard sex, race, and age model. CONCLUSIONS: If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters.

Fitting of bone mineral density with consideration of anthropometric parameters.

UNLABELLED: A new model describing normal values of bone mineral density in children has been evaluated, which includes not only the traditional parameters of age, gender, and race, but also weight, height, percent body fat, and sexual maturity. This model may constitute a better comparative norm for a specific child with given anthropometric values. INTRODUCTION: Previous descriptions of children's bone mineral density (BMD) by age have focused on segmenting diverse populations by race and gender without adjusting for anthropometric variables or have included the effects of anthropometric variables over a relatively homogeneous population. METHODS: Multivariate semi-metric smoothing (MS(2)) provides a way to describe a diverse population using a model that includes multiple effects and their interactions while producing a result that can be smoothed with respect to age in order to provide connected percentiles. We applied MS(2) to spine BMD data from the Bone Mineral Density in Childhood Study to evaluate which of gender, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's BMD values. By balancing high adjusted R (2) values and low mean square errors with clinical needs, a model using age, gender, race, weight, and percent body fat is proposed and examined. RESULTS: This model provides narrower distributions and slight shifts of BMD values compared to the traditional model, which includes only age, gender, and race. Thus, the proposed model might constitute a better comparative standard for a specific child with given anthropometric values and should be less dependent on the anthropometric characteristics of the cohort used to devise the model. CONCLUSIONS: The inclusion of multiple explanatory variables in the model, while creating smooth output curves, makes the MS(2) method attractive in modeling practically sized data sets. The clinical use of this model by the bone research community has yet to be fully established.

Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy.

UNLABELLED: We compared microarchitecture and mechanical competence parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element analysis of radius and tibia to those measured by histomorphometry, micro-CT, and finite-element analysis of transiliac bone biopsies. Correlations were weak to moderate between parameters measured on biopsies and scans. INTRODUCTION: HR-pQCT is a new imaging technique that assesses trabecular and cortical bone microarchitecture of the radius and tibia in vivo. The purpose of this study was to determine the extent to which microarchitectural variables measured by HR-pQCT reflect those measured by the "gold standard," transiliac bone biopsy. METHODS: HR-pQCT scans (Xtreme CT, Scanco Medical AG) and iliac crest bone biopsies were performed in 54 subjects (aged 39 +/- 10 years). Biopsies were analyzed by 2D quantitative histomorphometry and 3D microcomputed tomography (microCT). Apparent Young's modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (microFE) of biopsy microCT and HR-pQCT images. RESULTS: The strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by microCT of biopsies and HR-pQCT of the radius (R 0.365-0.522; P < 0.01). Cortical width of biopsies correlated with cortical thickness by HR-pQCT, but only at the tibia (R = 0.360, P < 0.01). Apparent Young's modulus calculated by microFE of biopsies correlated with that calculated for both radius (R = 0.442; P < 0.001) and tibia (R = 0.380; P < 0.001) HR-pQCT scans. CONCLUSIONS: The associations between peripheral (HR-pQCT) and axial (transiliac biopsy) measures of microarchitecture and estimated mechanical competence are significant but modest.

Transmenopausal changes in the trabecular bone structure.

INTRODUCTION: Post-menopausal osteoporosis is a disorder of excess skeletal fragility, due partly to changes in bone microstructure. Menopause is known to result in bone loss and reduction in bone mechanical strength. However, the mechanism and nature of microstructural changes at menopause need more detailed description and analyses. The overall hypothesis for this analysis is that the variables describing trabecular bone micro-architecture will be affected by changes in the hormonal status of women just prior to, and early after, last menses, and that volumetric bone density, and trabecular structure will decline significantly. The study was designed to capture true longitudinal transmenopausal changes in three-dimensional (3-D) trabecular bone architecture. Currently, minimal data exist regarding these features. MATERIALS AND METHODS: Transilial biopsies specimens were obtained from healthy pre-menopausal women (age >46), and repeated at 12 months after the last menstrual period. Bone architecture was quantified in 38 paired specimens using micro-computed tomography (micro-CT-40, Scanco) techniques. Bone biopsies were embedded for histomorphomteric analyses and parts of the analyses have been published elsewhere. Embedded bone biopsies were scanned at 30-mum resolution such that the region of interest was similar to that in the two-dimensional (2-D) histomorphometric analyses. Paired t-tests were used to compare the pre- and post-menopausal bone structural data from each technique. RESULTS: There was good correlation between standard histomorphometric (2-D) and micro-CT (3-D) measurements. Most of the variables characterizing bone structure in post-menopausal women (from micro-CT) significantly decreased (BV/TV, trabecular number, apparent and tissue density). In addition, both trabecular spacing (Tb.S) and the structure model index (SMI) increased in the post-menopausal women suggesting transformation of trabecular bone from plate- to rod-like structure. The 3-D trabecular connectivity density (Conn.D) was negatively correlated with activation frequency (Ac.f). CONCLUSIONS: These data suggest that 3-D micro-CT measurements (longitudinal) are comparable to those of standard histomorphometry, and that most of the bone structural measurements are sensitive to changes in women's hormonal status across menopause.

Pathophysiology of osteoporosis and fracture.

Bone is a vital, dynamic tissue that performs many functions, including a major role in serum homeostasis. A complex interplay of factors affects bone function and bone health. This article provides an overview of bone physiology and the pathophysiology of osteoporosis and fragility fracture. An understanding of the material presented here will provide a foundation to assess the bone health of individuals, to promote bone health, and to prevent fracture in patients of all ages.

Hormones, weight change and menopause.

OBJECTIVE: To determine total body weight change occurring in women at mid-life, specifically with respect to occurrence of menopause and use of estrogen. DESIGN: Retrospective analysis of body weight measurements accumulated in two cohorts of healthy women participating in studies of skeletal metabolism. SUBJECTS: Cohort 1: 191 healthy nuns enrolled in a prospective study of osteoporosis risk, aged 35-45 in 1967; cohort 2: 75 women aged 46 or older and still menstruating, enrolled in 1988 in a study of bone cell dynamics across menopause. Roughly one-third of each group received hormone replacement after menopause. MEASUREMENTS: Body weight and height, age, menstrual status and use of estrogen replacement. Cohort 1: 608 measurements at 5 y intervals spanning a period from 17 y before to 22 y after menopause; cohort 2: 1180 measurements at 6-month intervals spanning a period from 5 y prior to 5 y after menopause. RESULTS: In cohort 1 weight rose as a linear function of age (both chronological and menopausal), both before and after cessation of ovarian function, at a rate of approximately 0.43% y(-1). Neither the menopausal transition nor the use of estrogen had an appreciable effect on this rate of gain. In cohort 2 the rate of gain seemed to diminish slightly at menopause. As with cohort 1, hormone replacement (or its absence) had no appreciable effect on weight. CONCLUSIONS: The long-term, total body weight trajectory at mid-life is not influenced appreciably by either cessation of ovarian function or by hormone replacement.

The impact of lifestyle factors on stress fractures in female Army recruits.

Estimates are that stress fractures during basic training (BT) occur in as many as 14% of US female military recruits. Injuries of this type lead to morbidity ranging from minor pain to serious lifetime disability. Since women are assuming an increasing role in the military, this high risk of stress fracture is of concern. The purpose of this prospective study was to determine factors that predict stress fracture during BT in US Army female recruits. The analysis was part of an investigation using quantitative ultrasound (QUS) to determine risk of stress fracture during BT. Prior to the start of BT, we obtained QUS measurements and asked each subject to complete a risk factor questionnaire. We completed assessments for 3758 recruits who then proceeded to 8 weeks of BT, during which time any diagnosed stress fractures were reported to us by Army clinicians. Stress fractures were confirmed with radiographs. The incidence of stress fracture was 8.5% per 8 weeks. Factors associated with stress fracture include: QUS, age, race, alcohol and tobacco use, weight-bearing exercise, lowest adult weight, corticosteroid use, and, in white women only, use of depo-medroxyprogesterone acetate (DMPA). Women who fractured were older than women who remained fracture-free, and black women were less likely to sustain a fracture than whites and other races. Compared with their non-stress-fracture counterparts, recruits who developed stress fractures were more likely to report current or past smoking, alcoholic drinking of > 10 drinks/week, corticosteroid use and lower adult weight. A history of regular exercise was protective against stress fracture, and a longer history of exercise further decreased the relative risk of fracture. Although current weight was not associated with stress fracture, lowest adult weight was inversely related to the risk of fracture. We conclude that prevention of stress fractures in female military recruits should include a thorough assessment of lifestyle factors such as exercise patterns, alcohol and tobacco habits, and corticosteroid and DMPA use. Assessment of risk factors may be helpful in pinpointing female recruits who should have further evaluation of their bone health or additional preparation, such as gradual increases in physical activity, prior to being exposed to the rigor of BT.

Designer estrogen vs. hormone replacement therapy: the menopausal woman's dilemma.

Although hormone replacement therapy (HRT) has many proven health benefits for postmenopausal women, relatively few women are taking advantage of this option. A major reason for this is lack of understanding by women of the benefits and risks of using HRT. Additionally, many women are uninformed about "designer estrogens," more correctly known as Selective Estrogen Receptor Modulators (SERMs), as an alternative approach to the use of esrogen. One of the major challenges of contemporary nursing is to help women maintain optimum health and enjoy a high quality of life after menopause. One aspect of managing menopausal health is an understanding of the hormonal options available to women. The purpose of this article is to present a synthesis of information comparing HRT and SERMs so that the reader can help his/her clients make informed choices about replacement therapy.