ABBREVIATIONSAACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B ligand RCT = randomized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization.

BACKGROUND:To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.METHODS:In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.RESULTS:Thirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed.CONCLUSIONS:High-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.LEVEL OF EVIDENCE:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

This study compared microscopic magnetic resonance imaging (mu MRI) parameters of trabecular microarchitecture between postmenopausal women with and without fracture who have normal or osteopenic bone mineral density (BMD) on dual-energy X-ray absorptiometry (DXA). It included 36 postmenopausal white women 50 years of age and older with normal or osteopenic BMD (T-scores better than -2.5 at the lumbar spine, proximal femur, and one-third radius on DXA). Eighteen women had a history of low-energy fracture, whereas 18 women had no history of fracture and served as an age, race, and ultradistal radius BMD-matched control group. A three-dimensional fast large-angle spin-echo (FLASE) sequence with 137?mu m?x?137?mu m?x?400?mu m resolution was performed through the nondominant wrist of all 36 women using the same 1.5T scanner. The high-resolution images were used to measure trabecular bone volume fraction, trabecular thickness, surface-to-curve ratio, and erosion index. Wilcoxon signed-rank tests were used to compare differences in BMD and mu MRI parameters between postmenopausal women with and without fracture. Post-menopausal women with fracture had significantly lower (p?<?0.05) trabecular bone volume fraction and surface-to-curve ratio and significantly higher (p?<?0.05) erosion index than postmenopausal women without fracture. There was no significant difference between postmenopausal women with and without fracture in trabecular thickness (p?=?0.80) and BMD of the spine (p?=?0.21), proximal femur (p?=?0.19), one-third radius (p?=?0.47), and ultradistal radius (p?=?0.90). Postmenopausal women with normal or osteopenic BMD who had a history of low-energy fracture had significantly different (p?<?0.05) mu MRI parameters than an age, race, and ultradistal radius BMD-matched control group of postmenopausal women with no history of fracture. Our study suggests that mu MRI can be used to identify individuals without a DXA-based diagnosis of osteoporosis who have impaired trabecular microarchitecture and thus a heretofore-unappreciated elevated fracture risk. (c) 2012 American Society for Bone and Mineral Research.

▴ Alendronate/colecalciferol 70mg/2800IU, a once-weekly tablet containing the bisphosphonate alendronate and colecalciferol (the precursor of the biologically active form of vitamin D), has been approved for the treatment of osteoporosis in women and for increasing bone mass in men with osteoporosis. ▴ The mean oral bioavailability of alendronate or colecalciferol is similar when administered alone or as one once-weekly tablet containing alendronate/colecalciferol 70mg/2800IU. ▴ In a 15-week, randomized, double-blind, multicenter study in patients with osteoporosis, the proportion of patients with serum 25-hydroxyvitamin D3 levels <15 ng/mL was significantly lower with alendronate/colecalciferol than with alendronate alone. ▴ Markers of bone turnover were not significantly different in recipients of alendronate/colecalciferol or alendronate alone. ▴ Alendronate is generally well tolerated in men and women with osteoporosis, with adverse events being mainly transient and associated with the upper gastrointestinal tract. The treatment-related adverse event profile of once-weekly alendronate/colecalciferol 70mg/2800IU was similar to that of once-weekly alendronate in the 15-week, double-blind study in patients with osteoporosis.

Secondary osteoporosis results from medical conditions or treatments that interfere with the attainment of peak bone mass and/or may predispose to accelerated bone loss. Although secondary osteoporosis is less common, it is becoming more frequently diagnosed. Apart from the well-defined risk of secondary osteoporosis in patients requiring long-term corticosteroids therapy, an increasing list of dietary , lifestyle, endocrine, metabolic, and other causes of bone mass deterioration has been identified (Table 1). Recently it has been demonstrated that, in contrast to primary osteoporosis which is associated with age, gender, and family history, secondary osteoporosis shows a prevalence in men similar to that in women (men 21% versus women 17.5%) [1]. However, at presentation with a recent clinical vertebral or nonvertebral fracture, at least 27% of patients have previously unknown contributors to secondary osteoporosis, which are treatable or need follow-up [2]. Therefore, a careful medical examination always should be carried out in each patient with a recent fracture to exclude potentially reversible causes of bone loss. In comparison with primary osteoporosis, treatment of secondary osteoporosis is usually more complex and requires treating the underlying disease. The main focus of this special issue is on current research that advances our understanding of the mechanisms underlying the endocrine and metabolic causes of bone mass deterioration. In the paper " Bone mineral density accrual determines energy expenditure with refeeding in anorexia nervosa and supersedes return of menses, " the authors in the clinical study examined the disproportionate increase in resting energy expenditure that occurs with refeeding of women with anorexia nervosa to determine if it was related to bone mass increase. They found that prolonged nutritional rehabilitation may lead to recovery from osteopenia (a common finding in anorexia nervosa) and resumption of menses in the women who remain amenorrheic with low bone mineral density (BMD). The paper entitled " Protective role of black tea extract (BTE) against non-alcoholic steatohepatitis (NASH)-induced skeletal dysfunction " was aimed to examine the chemoprotective actions of aqueous BTE on decreased BMD induced by nonalcoholic steatohepatitis in the Wistar rats. Some previous studies have suggested that habitual tea consumption might have beneficial effect on BMD in adults. In this study, the authors confirmed this suggestion in rats and also found that BTE may influence levels of RANKL, osteoprotegerin, and bone turnover markers. The paper " Bone health in patients with multiple sclerosis " describes the up-to-date diagnostic criteria and includes detailed …

This paper focuses on humanitarian-architecture practices in hazard-prone environments. It highlights women's role in slum-upgrading, aided-self-help, incremental-housing and disaster-risk-reduction processes. We present the experiences of the seven shortlisted nominees to the first edition of the Marielle Franco Community-Design Award, which sought to acknowledge the long-lasting activities of professionals working within vulnerable communities. Although the award did not have a gender focus, all the shortlisted nominees were eventually either women architects or women-led architecture offices, mostly engaged with local NGOs assisting dwellers of fragile settlements while building their capacities. We sought to explore the distinctive features of their practices and how these contribute to improve communities' living conditions. Our research relied on a literature review and the comparative analysis of the profile, practice and achievements of the shortlisted nominees. Our study shows that the processes set forth by these professionals are as important as their architectural results. Furthermore, the outcomes of their work extrapolate the physical dimension to embrace long-term social impacts. By following an empathic and immersive approach in their relationship with the concerned people (in particular women), these female architects could plan, design and build in a truly collaborative mode.

Vitamin D is a “hot topic,” with the number of citations in PubMed exceeding 2400 in 2009, a 3-fold increase in 1 year. In the US, the number of requested 25-hydroxyvitamin D (25-OHD)9 assays is increasing exponentially. Not all of the published material has validity, however. A panel of experts was invited to address a series of questions pertaining to laboratory methods and clinical applications of available assays for 25-OHD and 1,25-dihydroxyvitamin D (1,25-OHD).What should we measure: 25-OHD3, 25-OHD2, both, or 1,25-OHD? Rosemary L. Schleicher: Our interest is in providing 25-OHD data for the National Health and Nutrition Examination Survey (NHANES). Separate estimates for 25-OHD2 and 25-OHD3—together with recent food- and supplement-intake data, questionnaire data about physical activity, sun-protection behavior and skin type, and demographic information related to race/ethnicity, season, latitude, and age—provide valuable information about the sources of vitamin D for those in the noninstitutionalized civilian US population. In addition, we will be separating and quantifying the C3 epimer of 25-OHD3, which may not be as biologically active as 25-OHD3.John Eisman: 25-OHD2 and 25-OHD3 should be measured in most clinical situations, although in many countries vitamin supplements and food fortification are moving from vitamin D2 to D3. I am unaware of clinical needs requiring knowing 25-OHD2 and 25-OHD3 separately, or the C3 epimer. There are few clinical situations where knowing the 1,25-OHD concentrations are clinically critical or overly helpful.Roger Bouillon: We need to know the combined concentration of 25-OHD3 and 25-OHD2 because both products can be converted into the active hormone 1,25-OHD. In countries where vitamin D2 supplementation is not available, the measurement of 25-OHD3 alone would be sufficient, since there is very …

μm x 137 μm x 400 μm voxel size. (B) Three-dimensional model of trabecular micro-architecture obtained using a semi-automated virtual bone biopsy system . Microscopic Magnetic Resonance Imaging (μMRI) Assessment of Trabecular Micro-Architecture in Non-Osteoporotic PostMenopausal Women With and Without Fracture Richard Kijowski, Michael Tuite, Diane Krueger, Michael Kleerekoper, and Neil Binkley Radiology, University of Wisconsin, Madison, Wisconsin, United States, Medicine, University of Wisconsin, Madison, Wisconsin, United States, Medicine, St. Joseph Mercy Reichert Health Center, Ypsilanti, Michigan, United States

OBJECTIVEOur objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement.EVIDENCEEach expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence.CONSENSUS PROCESSA consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors.CONCLUSIONSThe major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.

Purpose: In addition to bone mineral density (BMD), trabecular microstructure contributes to skeletal strength. Our goal was to examine changes in trabecular microstructure in women on therapy.Materials and methods: We followed 10 postmenopausal women receiving a bisphosphonate, risedronate (35 mg once weekly), over 12 months and examined trabecular microarchitecture with high resolution wrist MR images (hr-MRI). MRI parameters included bone volume/total volume (BV/TV), surface density (representing plates), curve density (representing rods), surface-to-curve ratio and erosion index (depicting deterioration). We assessed BMD of the spine, hip and radius and markers of bone turnover.Results: Women had been receiving bisphosphonate therapy for 43 9 months (mean +/- SD) prior to the first MRI. Indices of hr-MRI demonstrated improvement in surface-to-curve ratio (13.0%) and a decrease in erosion index (12.1%) consistent with less deterioration (both p<0.05). BMD of the spine, hip and radius and markers of bone turnover remained stable. Parameters of hr-MRI were associated with 1/3 distal radius BMD (correlation coefficient 0.71 to 0.86, p<0.05).Discussion: We conclude that hr-MRI of the radius demonstrates improvements in trabecular microstructure not appreciated by conventional BMD and provides additional information on parameters that contribute to structural integrity in patients on antiresorptive therapy. (C) 2010 Elsevier Inc. All rights reserved.

American Association of Clinical Endocrinologists

Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. Participants in Development of Scientific Statement: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunctionwiththeTaskForce,leadauthors(n25)andpeerreviewers(n13)foreachspecifictopicwereselected.Alldiscussions regardingcontentandgradingofevidenceoccurredviateleconferenceorelectronicandwrittencorrespondence.Nofundingwas provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence. Consensus Process: A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations Assessment, Development,andEvaluation)systemincommonusebyTheEndocrineSocietyforpreparingclinicalguidelines.Thefinaliteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors. Conclusions: The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms ofurogenitalatrophyandpreventionoffracturesanddiabetes.Risksincludedvenothromboticepisodes,stroke,andcholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, nonstatistically significant trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup,estrogenplussomeprogestogensincreasedtheriskofbreastcancer,whereasestrogenalonedidnot.Beneficialeffects oncolorectalandendometrialcancerandharmfuleffectsonovariancanceroccurredbutaffectedonlyasmallnumberofwomen. Data from the various Women’s Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.

In 1994, the WHO published a detailed report that was developed over a number of years by an international group of experts in osteoporosis [1]. This work formalized the current prefracture diagnos...

Evidence-based guidelines that have been prepared by many professional organizations aimed at assisting the clinician in the initial evaluation of postmenopausal women who should be considered for bone mineral density evaluation by dual-energy x-ray absorptiometry; history, physical examination, and laboratory testing in those women being considered for pharmacologic intervention; and monitoring and management of women for whom therapy is prescribed are discussed.

This is a review article designed to address the effects of soy isoflavones on bone metabolism in postmenopausal women and their place in the prevention and treatment of postmenopausal osteoporosis. Soy isoflavones are natural products that could be used as an alternative to menopausal hormone therapy because they are structurally and functionally related to 17beta-estradiol. In vitro and animal studies have shown that they act in multiple ways to exert their bone-supporting effects. They act on both osteoblasts and osteoclasts through genomic and nongenomic pathways. Epidemiological studies and clinical trials suggest that soy isoflavones have beneficial effects on bone mineral density, bone turnover markers, and bone mechanical strength in postmenopausal women. However, there are conflicting results related to differences in study design, estrogen status of the body, metabolism of isoflavones among individuals, and other dietary factors. The long-term safety of soy isoflavone supplements remains to be demonstrated.

Purpose of review To present an overview of the peer-reviewed literature relating to glucocorticoid-induced osteoporosis that has been published since January 2006. Recent findings Understanding the pathophysiology of bone loss resulting from glucocorticoid use has become clearer. The role of the receptor-activated nuclear factor κB–ligand–osteoprotogerin system has been clarified and will likely lead to better targeted therapies. Minimal trauma fractures occur in patients treated with glucocorticoids at higher bone mineral density than is seen with other primary or secondary causes of osteoporosis. Uncertainty still remains about the lowest dose of glucocorticoids that is not associated with bone loss. Bisphosphonates remain the treatment of choice for glucocorticoid-induced osteoporosis, but despite this effective therapy the disease remains under recognized and undertreated. Summary Glucocorticoid-induced osteoporosis is a leading cause of secondary osteoporosis, one of the more devastating consequences of glucocorticoid therapy. Bone mineral density underestimates the risk of fragility fractures in glucocorticoid-induced osteoporosis, which may account for the underrecognition and undertreatment of the disease prior to fracture.

PURPOSE OF REVIEW:To present an overview of the peer-reviewed literature relating to glucocorticoid-induced osteoporosis that has been published since January 2006.RECENT FINDINGS:Understanding the pathophysiology of bone loss resulting from glucocorticoid use has become clearer. The role of the receptor-activated nuclear factor kappaB-ligand-osteoprotogerin system has been clarified and will likely lead to better targeted therapies. Minimal trauma fractures occur in patients treated with glucocorticoids at higher bone mineral density than is seen with other primary or secondary causes of osteoporosis. Uncertainty still remains about the lowest dose of glucocorticoids that is not associated with bone loss. Bisphosphonates remain the treatment of choice for glucocorticoid-induced osteoporosis, but despite this effective therapy the disease remains under recognized and undertreated.SUMMARY:Glucocorticoid-induced osteoporosis is a leading cause of secondary osteoporosis, one of the more devastating consequences of glucocorticoid therapy. Bone mineral density underestimates the risk of fragility fractures in glucocorticoid-induced osteoporosis, which may account for the underrecognition and undertreatment of the disease prior to fracture.

Recent advances in osteoporosis have dramatically changed the management and treatment of this disease. This article reviews the safety and efficacy of US FDA-approved drugs for prevention and treatment of postmenopausal osteoporosis, as well as studies on combination, sequential or intermittent use of these agents. A review of promising agents for osteoporosis therapy is provided.