Journal of Osteoporosis The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. An Evaluative History of Bisphosphonate Drugs: Dual Physiologic Effects of Pyrophosphate as Inspiration for a Novel Pharmaceutical Class Wed, 05 Oct 2016 09:26:36 +0000 The documented history of the development of the bisphosphonate drugs is reviewed in sufficient detail to permit independent evaluation of the consistency of the conclusions reached from the available data. The evidence developed during the early interval of these studies 1960–1975 was sufficient to establish that pyrophosphate shares the subsequently established dual bisphosphonate characteristics of bone resorption inhibition and prevention of tissue mineralization. W. Banks Hinshaw and Allyn F. DeLong Copyright © 2016 W. Banks Hinshaw and Allyn F. DeLong. All rights reserved. Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status Thu, 08 Sep 2016 09:30:43 +0000 Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD) was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular) and 2 diaphyseal (mainly cortical)). BMD at femoral neck (FN) and lumbar spine L2–4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH), and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of and scores and for biochemical measurements. Results. Low BMD scores were found at metaphyseal regions in the leg () and in the FN (). The distal metaphyseal region BMD in the leg was lower than spine or FN (). PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD scores were associated with body weight (), but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight. Michael W. J. Davie, Sally F. Evans, and Christopher A. Sharp Copyright © 2016 Michael W. J. Davie et al. All rights reserved. The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism Wed, 24 Aug 2016 17:56:05 +0000 Although it is recognized that the mechanical stresses associated with physical activity augment bone mineral density and improve bone quality, our understanding of how exercise modulates bone homeostasis at the molecular level is lacking. In a before and after trial involving 43 healthy adults, we measured the effect of six months of supervised exercise training on the spontaneous and phytohemagglutinin-induced production of osteoclastogenic cytokines (interleukin-1α, tumor necrosis factor-α), antiosteoclastogenic cytokines (transforming growth factor-β1 and interleukins 4 and 10), pleiotropic cytokines with variable effects on osteoclastogenesis (interferon-γ, interleukin-6), and T cell growth and differentiation factors (interleukins 2 and 12) by peripheral blood mononuclear cells. We also measured lymphocyte phenotypes and serum markers of bone formation (osteocalcin), bone resorption (C-terminal telopeptides of Type I collagen), and bone homeostasis (25 (OH) vitamin D, estradiol, testosterone, parathyroid hormone, and insulin-like growth factor 1). A combination of aerobic, resistance, and flexibility exercises done on average of 2.5 hours a week attenuated the production of osteoclastogenic cytokines and enhanced the production of antiosteoclastogenic cytokines. These changes were accompanied by a 16% reduction in collagen degradation products and a 9.8% increase in osteocalcin levels. We conclude that long-term moderate intensity exercise exerts a favorable effect on bone resorption by changing the balance between blood mononuclear cells producing osteoclastogenic cytokines and those producing antiosteoclastogenic cytokines. This trial is registered with Clinical Identifier: NCT02765945. J. Kelly Smith, Rhesa Dykes, and David S. Chi Copyright © 2016 J. Kelly Smith et al. All rights reserved. Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis Mon, 08 Aug 2016 12:12:45 +0000 The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed. A. Sánchez, L. R. Brun, H. Salerni, P. R. Costanzo, D. González, A. Bagur, B. Oliveri, M. B. Zanchetta, V. Farías, L. Maffei, V. Premrou, J. L. Mansur, M. S. Larroudé, M. A. Sarli, P. Rey, M. R. Ulla, M. M. Pavlove, S. Karlsbrum, and M. L. Brance Copyright © 2016 A. Sánchez et al. All rights reserved. Sclerostin Antibody Therapy for the Treatment of Osteoporosis: Clinical Prospects and Challenges Thu, 26 May 2016 08:38:41 +0000 It is estimated that over 200 million adults worldwide have osteoporosis, a disease that has increasing socioeconomic impact reflected by unsustainable costs associated with disability, fracture management, hospital stays, and treatment. Existing therapeutic treatments for osteoporosis are associated with a variety of issues relating to use, clinical predictability, and health risks. Consequently, additional novel therapeutic targets are increasingly sought. A promising therapeutic candidate is sclerostin, a Wnt pathway antagonist and, as such, a negative regulator of bone formation. Sclerostin antibody treatment has demonstrated efficacy and superiority compared to other anabolic treatments for increasing bone formation in both preclinical and clinical settings. Accordingly, it has been suggested that sclerostin antibody treatment is set to achieve market approval by 2017 and aggressively compete as the gold standard for osteoporotic treatment by 2021. In anticipation of phase III trial results which may potentially signify a significant step in achieving market approval here, we review the preclinical and clinical emergence of sclerostin antibody therapies for both osteoporosis and alternative applications. Potential clinical challenges are also explored as well as ongoing developments that may impact on the eventual clinical application of sclerostin antibodies as an effective treatment of osteoporosis. Claire MacNabb, D. Patton, and J. S. Hayes Copyright © 2016 Claire MacNabb et al. All rights reserved. Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy Thu, 12 May 2016 09:05:17 +0000 Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance () and leptin () and a positive correlation with adiponectin were found (). The best set of predictors for TBS values at baseline were female sex (), age (), and BMI (). The best set of predictors for TBS following 6 months of biologic therapy were age (), BMI (), and serum adiponectin levels (). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy. José L. Hernández, Raquel López-Mejías, Ricardo Blanco, Trinitario Pina, Sheila Ruiz, Isabel Sierra, Begoña Ubilla, Verónica Mijares, Marcos A. González-López, Susana Armesto, Alfonso Corrales, Enar Pons, Patricia Fuentevilla, Carmen González-Vela, and Miguel Á. González-Gay Copyright © 2016 José L. Hernández et al. All rights reserved. Cross-Calibration of GE Healthcare Lunar Prodigy and iDXA Dual-Energy X-Ray Densitometers for Bone Mineral Measurements Wed, 27 Apr 2016 07:50:16 +0000 In long-term prospective studies, dual-energy X-ray absorptiometry (DXA) devices need to be inevitably changed. It is essential to assess whether systematic differences will exist between measurements with the new and old device. A group of female volunteers (21–72 years) underwent anteroposterior lumbar spine L2–L4 (), proximal femur (), and total body () measurements with the Prodigy and the iDXA scanners at the same visit. The bone mineral density (BMD) measurements with these two scanners showed a high linear association at all tested sites (; ). The average iDXA BMD values were 1.5%, 0.5%, and 0.9% higher than those of Prodigy for lumbar spine (L2–L4) (), femoral neck (), and total hip (), respectively. Total body BMD values measured with the iDXA were −1.3% lower () than those measured with the Prodigy. For total body, lumbar spine, and femoral neck, the BMD differences as measured with these two devices were independent of subject height and weight. Linear correction equations were developed to ensure comparability of BMD measurements obtained with both DXA scanners. Importantly, use of equations from previous studies would have increased the discrepancy between these particular DXA scanners, especially at hip and at spine. J. Saarelainen, M. Hakulinen, T. Rikkonen, H. Kröger, M. Tuppurainen, H. Koivumaa-Honkanen, R. Honkanen, M. Hujo, and J. S. Jurvelin Copyright © 2016 J. Saarelainen et al. All rights reserved. Bone Mineral Density in Postmenopausal Women Heterozygous for the C282Y HFE Mutation Thu, 31 Mar 2016 17:49:25 +0000 Mutations in the HFE gene may be associated with increased tissue iron stores reflected in an elevated serum ferritin. With homozygous mutation C282Y, the increase in serum ferritin may be associated with tissue damage in the liver, pancreas, and pituitary and with a reduced bone mineral density. With heterozygous mutation C282Y, the degree of iron retention is less but information relating to how a heterozygous C282Y mutation might impact bone mineral density is uncertain. The present study was undertaken to study the relationships between bone mineral density measured by dual energy X-ray absorptiometry and the serum ferritin and serum iron in postmenopausal women heterozygous for the C282Y mutation. The spinal bone mineral density, L2–4, was significantly less than age matched community controls (). There was no significant change in the femoral neck bone mineral density compared to age matched community controls. The correlation between the spinal bone mineral density, L2–4, the femoral neck bone mineral density, and the serum ferritin was not significant. The serum iron correlated significantly inversely with the femoral neck bone mineral density (). The heterozygous C282Y mutation may be associated with impairment of bone cell function in postmenopausal women when only small increases in the serum iron or serum ferritin have occurred. Jenny E. Gunton, Frances Gates, Greg R. Fulcher, and Phillip B. Clifton-Bligh Copyright © 2016 Jenny E. Gunton et al. All rights reserved. Bone Strength and Arterial Stiffness Impact on Cardiovascular Mortality in a General Population Mon, 07 Mar 2016 14:41:29 +0000 Osteoporosis and increased arterial stiffness independently have been found to be associated with higher cardiovascular events rates in the general population (GP). We examined 558 patients from GP by dual-energy X-ray absorptiometry (DXA) and pulse wave velocity (PWV) measurements at baseline, with 36-month follow-up period. DXA assessed bone mineral density of femoral neck (BMD FN) and lumbar spine (BMD LS). Carotid-femoral PWV was assessed by pulsed-Doppler. The aim of our study is to find correlation between bone strength and arterial stiffness and their impact on cardiovascular mortality in GP. The mean ± SD of BMD FN, BMD LS, and PWV was  g/cm2,  g/cm2, and  m/s. In multiple regression analysis we found BMD FN (βst , ), hypertension (βst = 1.7340, ), and diabetes (, ). With Cox-regression analysis, after 17 cardiovascular events, the significant covariates retained by the backward model were BMD FN (, ) and PWV (, ). The cut-off values were PWV = 9.4 m/s, BMD FN = 0.783 g/cm2, and BMD LS = 0.992 g/cm2. The results for BMD FN and PWV hazard ratio risk were 1.116 and 1.297, respectively. BMD FN as a measure of bone strength and PWV as a measure of arterial stiffness are strong independent predictors of cardiovascular mortality in GP. Petar Avramovski, Maja Avramovska, and Aleksandar Sikole Copyright © 2016 Petar Avramovski et al. All rights reserved. Understanding Referral Patterns for Bone Mineral Density Testing among Family Physicians: A Qualitative Descriptive Study Tue, 19 Jan 2016 16:21:59 +0000 Introduction. Evidence of inappropriate bone mineral density (BMD) testing has been identified in terms of overtesting in low risk women and undertesting among patients at high risk. In light of these phenomena, the objective of this study was to understand the referral patterns for BMD testing among Ontario’s family physicians (FPs). Methods. A qualitative descriptive approach was adopted. Twenty-two FPs took part in a semi-structured interview lasting approximately 30 minutes. An inductive thematic analysis was performed on the transcribed data in order to understand the referral patterns for BMD testing. Results. We identified a lack of clarity about screening for osteoporosis with a tendency for baseline BMD testing in healthy, postmenopausal women and a lack of clarity on the appropriate age for screening for men in particular. A lack of clarity on appropriate intervals for follow-up testing was also described. Conclusions. These findings lend support to what has been documented at the population level suggesting a tendency among FPs to refer menopausal women (at low risk). Emphasis on referral of high-risk groups as well as men and further clarification and education on the appropriate intervals for follow-up testing is warranted. Sarah E. P. Munce, Sonya Allin, Leslie Carlin, Joanna Sale, Gillian Hawker, Sandra Kim, Debra A. Butt, Irene Polidoulis, Karen Tu, and Susan B. Jaglal Copyright © 2016 Sarah E. P. Munce et al. All rights reserved. The Effects of Noncompliance to Prolia (Denosumab) on the Changes in Bone Mineral Density: A Retrospective Review Mon, 04 Jan 2016 12:48:25 +0000 Although denosumab (Prolia) has been shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials, few studies have determined its effectiveness in real world clinical practice. A retrospective review of patients prescribed Prolia assessing the impact that noncompliance from the regular dosing regimen of six months for denosumab has on bone mineral density (BMD) was performed. 924 patient records were reviewed between August 2012 and September 2013 with 436 patients meeting the eligibility criteria. Patients were divided into three groups: subsequent injection of denosumab (1) less than five months, (2) between five and seven months, and (3) more than seven months after their initial subcutaneous injection. A multivariable regression analysis was conducted comparing the differences among the three prespecified groups in BMD change (g/cm2) after one year of denosumab therapy at both the lumbar spine (LS) and femoral neck (FN). The differences in LS and FN BMD have shown that the relationship between the timing of drug administration in these three groups and change in BMD over 1 year was not clinically or statistically significant (). A follow-up study with a larger sample size and longer follow-up duration is required to further characterize this relationship. Matthew Wong-Pack, Aashish Kalani, Jacob Hordyk, George Ioannidis, Robert Bensen, William G. Bensen, Alexandra Papaioannou, Jonathan D. Adachi, and Arthur N. Lau Copyright © 2016 Matthew Wong-Pack et al. All rights reserved. Denosumab for Elderly Men with Osteoporosis: A Cost-Effectiveness Analysis from the US Payer Perspective Wed, 09 Dec 2015 11:18:44 +0000 Purpose. To evaluate the cost-effectiveness of denosumab versus other osteoporotic treatments in older men with osteoporosis from a US payer perspective. Methods. A lifetime cohort Markov model previously developed for postmenopausal osteoporosis (PMO) was used. Men in the model were 78 years old, with a BMD -score of −2.12 and a vertebral fracture prevalence of 23%. During each 6-month Markov cycle, patients could have experienced a hip, vertebral or nonhip, nonvertebral (NHNV) osteoporotic fracture, remained in a nonfracture state, remained in a postfracture state, or died. Background fracture risks, mortality rates, persistence rates, health utilities, and medical and drug costs were derived from published sources. Previous PMO studies were used for drug efficacy in reducing fracture risk. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, risedronate, ibandronate, teriparatide, and zoledronate. Results. Denosumab had an incremental cost-effectiveness ratio (ICER) of $16,888 compared to generic alendronate and dominated all other treatments. Results were most sensitive to changes in costs of denosumab and the relative risk of hip fracture. Conclusion. Despite a higher annual treatment cost compared to other medications, denosumab is cost-effective compared to other osteoporotic treatments in older osteoporotic US men. Stuart Silverman, Irene Agodoa, Morgan Kruse, Anju Parthan, and Eric Orwoll Copyright © 2015 Stuart Silverman et al. All rights reserved. The Impact of Fracture Incidence on Health Related Quality of Life among Community-Based Postmenopausal Women Thu, 30 Jul 2015 11:20:07 +0000 This prospective study aimed to examine the impact of fracture incidence on health-related quality of life (HRQOL) among postmenopausal women. Study subjects were Australian female community-dwellers in the Global Longitudinal Study of Osteoporosis in Women (GLOW). Self-administered questionnaires were collected annually from 2007 to 2010. Outcomes were the Medical Outcomes Study Short Form-36 (SF-36 physical function (SF36PFS) and vitality (SF36VS) scores), European Quality of Life (EQ-5D), and self-reported general health (GH) of excellent/good. Questionnaires were divided into prior to, the 1st, the 2nd, and the 3rd year after incident fracture assessments. Generalized linear models with generalised estimating equations (GEE) were employed for the analysis. The 2,872 participants (age: median 65; interquartile range 60–73 years) provided a total of 10,436 assessments including 266, 165 and 76 assessments for the 1st, the 2nd, and the 3rd year after incident fracture, respectively. Multivariate adjustments showed reductions in HRQOL measures peaking at the 1st year for SF36VS (coefficient −3.0; 95% CI: −5.1, −0.8) and EQ-5D (coefficient −0.03; 95% CI: −0.06, −0.00) and at the 2nd year for SF36PFS (coefficient −3.0; 95% CI: −5.6, −0.5) and GH (odds ratio 0.92; 95% CI: 0.70, 1.19). Fracture incidence reduced HRQOL including vitality and physical function among relatively young, healthy postmenopausal women and the reduction in European Quality of Life measure was clinically important. A. L. Barcenilla-Wong, J. S. Chen, M. J. Cross, and L. M. March Copyright © 2015 A. L. Barcenilla-Wong et al. All rights reserved. Posthospital Discharge Medical Care Costs and Family Burden Associated with Osteoporotic Fracture Patients in China from 2011 to 2013 Sun, 28 Jun 2015 14:08:12 +0000 Objectives. This study collected and evaluated data on the costs of outpatient medical care and family burden associated with osteoporosis-related fracture rehabilitation following hospital discharge in China. Materials and Methods. Data were collected using a patient questionnaire from osteoporosis-related fracture patients (N = 123) who aged 50 years and older who were discharged between January 2011 and January 2013 from 3 large hospitals in China. The survey captured posthospital discharge direct medical costs, indirect medical costs, lost work time for caregivers, and patient ambulatory status. Results. Hip fracture was the most frequent fracture site (62.6%), followed by vertebral fracture (34.2%). The mean direct medical care costs per patient totaled 3,910¥, while mean indirect medical costs totaled 743¥. Lost work time for unpaid family caregivers was 16.4 days, resulting in an average lost income of 3,233¥. The average posthospital direct medical cost, indirect medical cost, and caregiver lost income associated with a fracture patient totaled 7,886¥. Patients’ ambulatory status was negatively impacted following fracture. Conclusions. Significant time and cost of care are placed on patients and caregivers during rehabilitation after discharge for osteoporotic fracture. It is important to evaluate the role and responsibility for creating the growing and inequitable burden placed on patients and caregivers following osteoporotic fracture. Zhao Xie, Russel Burge, Yicheng Yang, Fen Du, Tie Lu, Qiang Huang, Wenyu Ye, and Weihua Xu Copyright © 2015 Zhao Xie et al. All rights reserved. Oral Calcidiol Is More Effective Than Cholecalciferol Supplementation to Reach Adequate 25(OH)D Levels in Patients with Autoimmune Diseases Chronically Treated with Low Doses of Glucocorticoids: A “Real-Life” Study Mon, 01 Jun 2015 12:45:19 +0000 Glucocorticoids (GCs) are the cornerstone of the therapy in many autoimmune and inflammatory diseases. However, it is well known that their use is a double edged sword, as their beneficial effects are associated almost universally with unwanted effects, as, for example glucocorticoid-induced osteoporosis (GIO). Over the last years, several clinical practice guidelines emphasize the need of preventing bone mass loss and reduce the incidence of fractures associated with GC use. Calcium and vitamin D supplementation, as adjunctive therapy, are included in all the practice guidelines. However, no standard vitamin D dose has been established. Several studies with postmenopausal women show that maintaining the levels above 30–33 ng/mL help improve the response to bisphosphonates. It is unknown if the response is the same in GIO, but in the clinical practice the levels are maintained at around the same values. In this study we demonstrate that patients with autoimmune diseases, undergoing glucocorticoid therapy, often present suboptimal 25(OH)D levels. Patients with higher body mass index and those receiving higher doses of glucocorticoids are at increased risk of having lower levels of 25(OH)D. In these patients, calcidiol supplementations are more effective than cholecalciferol to reach adequate 25(OH)D levels. Miguel Ortego-Jurado, José-Luis Callejas-Rubio, Raquel Ríos-Fernández, Juan González-Moreno, Amanda Rocío González Ramírez, Miguel A. González-Gay, and Norberto Ortego-Centeno Copyright © 2015 Miguel Ortego-Jurado et al. All rights reserved. Association of MRS-Based Vertebral Bone Marrow Fat Fraction with Bone Strength in a Human In Vitro Model Sun, 19 Apr 2015 11:14:28 +0000 Bone marrow adiposity has recently gained attention due to its association with bone loss pathophysiology. In this study, ten vertebrae were harvested from fresh human cadavers. Trabecular BMD and microstructure parameters were extracted from MDCT. Bone marrow fat fractions were determined using single-voxel MRS. Failure load (FL) values were assessed by destructive biomechanical testing. Significant correlations () were observed between MRS-based fat fraction and MDCT-based parameters (up to ) and MRS-based fat fraction and FL (). These findings underline the importance of the bone marrow in the pathophysiology and imaging diagnostics of osteoporosis. Dimitrios C. Karampinos, Stefan Ruschke, Olga Gordijenko, Eduardo Grande Garcia, Hendrik Kooijman, Rainer Burgkart, Ernst J. Rummeny, Jan S. Bauer, and Thomas Baum Copyright © 2015 Dimitrios C. Karampinos et al. All rights reserved. Type 1 Diabetes and Osteoporosis: From Molecular Pathways to Bone Phenotype Sun, 22 Mar 2015 12:40:49 +0000 The link between type 1 diabetes mellitus (DM1) and osteoporosis, identified decades ago, has gained attention in recent years. While a number of cellular mechanisms have been postulated to mediate this association, it is now established that defects in osteoblast differentiation and activity are the main culprits underlying bone fragility in DM1. Other contributing factors include an accumulation of advanced glycation end products (AGEs) and the development of diabetes complications (such as neuropathy and hypoglycemia), which cause further decline in bone mineral density (BMD), worsening geometric properties within bone, and increased fall risk. As a result, patients with DM1 have a 6.9-fold increased incidence of hip fracture compared to controls. Despite this increased fracture risk, bone fragility remains an underappreciated complication of DM1 and is not addressed in most diabetes guidelines. There is also a lack of data regarding the efficacy of therapeutic strategies to treat osteoporosis in this patient population. Together, our current understanding of bone fragility in DM1 calls for an update of diabetes guidelines, better screening tools, and further research into the use of therapeutic strategies in this patient population. Tayyab S. Khan and Lisa-Ann Fraser Copyright © 2015 Tayyab S. Khan and Lisa-Ann Fraser. All rights reserved. Associations of Polyunsaturated Fatty Acid Intake with Bone Mineral Density in Postmenopausal Women Tue, 17 Feb 2015 10:49:04 +0000 A secondary analysis of cross-sectional data was analyzed from 6 cohorts (Fall 1995–Fall 1997) of postmenopausal women (; years) participating in the Bone Estrogen Strength Training (BEST) study (a 12-month, block-randomized, clinical trial). Bone mineral density (BMD) was measured at femur neck and trochanter, lumbar spine (L2–L4), and total body BMD using dual-energy X-ray absorptiometry (DXA). Mean dietary polyunsaturated fatty acids (PUFAs) intakes were assessed using 8 days of diet records. Multiple linear regression was used to examine associations between dietary PUFAs and BMD. Covariates included in the models were total energy intake, body weight at year 1, years after menopause, exercise, use of hormone therapy (HT), total calcium, and total iron intakes. In the total sample, lumbar spine and total body BMD had significant negative associations with dietary PUFA intake at . In the non-HT group, no significant associations between dietary PUFA intake and BMD were seen. In the HT group, significant inverse associations with dietary PUFA intake were seen in the spine, total body, and Ward’s triangle BMD, suggesting that HT may influence PUFA associations with BMD. This study is registered with, identifier: NCT00000399. Margaret Harris, Vanessa Farrell, Linda Houtkooper, Scott Going, and Timothy Lohman Copyright © 2015 Margaret Harris et al. All rights reserved. Whole-Body Electromyostimulation to Fight Osteopenia in Elderly Females: The Randomized Controlled Training and Electrostimulation Trial (TEST-III) Sun, 15 Feb 2015 07:03:55 +0000 Whole-body electromyostimulation (WB-EMS) has been shown to be effective in increasing muscle strength and mass in elderly women. Because of the interaction of muscles and bones, these adaptions might be related to changes in bone parameters. 76 community-living osteopenic women 70 years and older were randomly assigned to either a WB-EMS group () or a control group (CG: ). The WB-EMS group performed 3 sessions every 14 days for one year while the CG performed gymnastics containing identical exercises without EMS. Primary study endpoints were bone mineral density (BMD) at lumbar spine (LS) and total hip (thip) as assessed by DXA. After 54 weeks of intervention, borderline nonsignificant intergroup differences were determined for LS-BMD (WB-EMS: % versus CG %, ) but not for thip-BMD (WB-EMS: % versus CG: %, ). With respect to secondary endpoints, there was a gain in lean body mass (LBM) of 1.5% () and an increase in grip strength of 8.4% () in the WB-EMS group compared to CG. WB-EMS effects on bone are less pronounced than previously reported effects on muscle mass. However, for subjects unable or unwilling to perform intense exercise programs, WB-EMS may be an option for maintaining BMD at the LS. Simon von Stengel, Michael Bebenek, Klaus Engelke, and Wolfgang Kemmler Copyright © 2015 Simon von Stengel et al. All rights reserved. Association of Bone Loss with the Upregulation of Survival-Related Genes and Concomitant Downregulation of Mammalian Target of Rapamycin and Osteoblast Differentiation-Related Genes in the Peripheral Blood of Late Postmenopausal Osteoporotic Women Tue, 10 Feb 2015 08:52:55 +0000 We aimed to identify bone related markers in the peripheral blood of osteoporotic (OP) patients that pointed toward molecular mechanisms underlying late postmenopausal bone loss. Whole blood from 22 late postmenopausal OP patients and 26 healthy subjects was examined. Bone mineral density (BMD) was measured by DXA. Protein levels of p70-S6K, p21, MMP-9, TGFβ1, and caspase-3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. OP registered by low BMD indices in late postmenopausal patients was associated with a significant upregulation of autophagy protein ULK1, cyclin-dependent kinase inhibitor p21, and metalloproteinase MMP-9 gene expression in the blood compared to the healthy controls and in a significant downregulation of mTOR (mammalian target of rapamycin), RUNX2, and ALPL gene expression, while expression of cathepsin K, caspase-3, transforming growth factor (TGF)β1, interleukin- (IL-) 1β, and tumor necrosis factor α (TNFα) was not significantly affected. We also observed a positive correlation between TGFβ1 and RUNX2 expression and BMD at femoral sites in these patients. Therefore, bone loss in late postmenopausal OP patients is associated with a significant upregulation of survival-related genes (ULK1 and p21) and MMP-9, as well as the downregulation of mTOR and osteoblast differentiation-related genes (RUNX2 and ALPL) in the peripheral blood compared to the healthy controls. Elena V. Tchetina, Karina A. Maslova, Mikhail Y. Krylov, and Valery A. Myakotkin Copyright © 2015 Elena V. Tchetina et al. All rights reserved. The Most Cited Papers in Osteoporosis and Related Research Sat, 31 Jan 2015 09:10:55 +0000 Osteoporosis is a systemic disease of the bone that affects millions of people and causes burden for both the affected individual and health systems and societies worldwide. Since the 1970s much research has been done in the field of osteoporosis. The number of citations of a paper reflects its influence and importance to the field. Thomson ISI Web of Science database was searched to retrieve a list of the fifty most cited articles related to osteoporosis and its research. The fifty most cited articles in absolute numbers in the field of osteoporosis were cited from 877 to 3056 times (mean ). Most papers were published in the basic science category . 395 authors contributed; a single paper had between one and 62 authors (mean: authors). 12 authors (3.04%) contributed between 7 and 4 papers; 340 authors (86.1%) were at least named once. Corresponding authors were from eight countries with most contributions from the United States (, 68%). The majority of papers were published in the 1990s . The list of 50 most cited papers presents citation classics in the field of osteoporosis and related research. Lukas A. Holzer, Andreas Leithner, and Gerold Holzer Copyright © 2015 Lukas A. Holzer et al. All rights reserved. Characterizing the Assessment and Management of Vitamin D Levels in Patients with Osteoporosis in Clinical Practice: A Chart Review Initiative Thu, 29 Jan 2015 09:47:07 +0000 Though vitamin D is important for bone health, little is known about the monitoring and management of vitamin D levels in patients with osteoporosis in clinical practice—a deficit this chart review initiative aimed to remedy. A total of 52 physicians completed profiles for 983 patients being treated for osteoporosis between November 2008 and April 2009. Information collected included demographics; fracture risk factors; availability and level of serum vitamin D measurements; and information on osteoporosis medications and calcium and vitamin D supplementation. Physicians also evaluated patients’ current regimens and detailed proposed changes, if applicable. Nearly 85% of patients were prescribed calcium and vitamin D supplements. Serum 25-hydroxy vitamin D levels were available for 73% of patients. Of these patients, approximately 50% had levels less than 80 nmol/L, which contrasts with the 37% thought to have “unsatisfactory” vitamin D levels based on physician perceptions. Physicians felt 26% of patients would benefit from additional vitamin D supplementation. However, no changes to the osteoporosis regimen were suggested for 48% of patients perceived to have “unsatisfactory” vitamin D levels. The results underscore the importance of considering vitamin D status when looking to optimize bone health. Jonathan D. Adachi, Jacques P. Brown, and George Ioannidis Copyright © 2015 Jonathan D. Adachi et al. All rights reserved. Treatment for Osteoporosis among Women in Japan: Associations with Patient Characteristics and Patient-Reported Outcomes in the 2008–2011 Japan National Health and Wellness Surveys Tue, 23 Dec 2014 06:54:11 +0000 This study was conducted to identify characteristics associated with treatment for osteoporosis among women aged 50 years and older in Japan and to explore differences among patients according to treatment regimen. Data were provided by a large annual survey representative of Japanese aged 18 and older; all measures were by self-report. Women aged 50 and older who reported diagnosed osteoporosis () were compared based on current treatment status using bivariate statistics and logistic regression. Approximately 1 in 3 women in this study reporting diagnosed osteoporosis were currently untreated. Factors associated with current treatment for osteoporosis included having ≥1 physician visit in the prior 6 months (OR = 5.4, ), self-rated moderate or severe osteoporosis (OR = 2.8, ), completion of menopause (OR = 1.6, ), and family history of osteoporosis (OR = 1.5, ), while longer duration of osteoporosis diagnosis (OR = 0.9, ) and arthritis (OR = 0.7, ) were associated with lower odds of treatment. These findings suggest that diagnosed patients are not being actively managed in the longer term, and efforts need to be made to ensure that patients stay engaged with their healthcare providers. Masayo Sato, Jeffrey Vietri, Jennifer A. Flynn, and Saeko Fujiwara Copyright © 2014 Masayo Sato et al. All rights reserved. Improving Hip Fracture Care in Ireland: A Preliminary Report of the Irish Hip Fracture Database Mon, 08 Dec 2014 12:34:35 +0000 Introduction. Hip fractures are common injuries in the older persons, with significant associated morbidity and mortality. The Irish Hip Fracture Database (IHFD) was implemented to monitor standards of care against international standards. Methods. The IHFD is a clinically led web-based audit. We summarize the data collected on hip fractures from April 2012 to March 2013 from 8 centres. Results. There were 843 patients with the majority being (70%) female. The 80–89-year age group accounted for the majority of fractures (44%). Most (71%) sustained a fall at home. Intertrochanteric fractures (40%) were most common. Only 28% were admitted to an orthopaedic ward within 4 hours. The majority (97%) underwent surgery with 44% having surgery within 36 hours. Medical optimization (35%) and lack of theatre space (26%) accounted for most of the surgical delay. While 29% were discharged home, 33% were discharged to a nursing home or other long-stay facilities. There was a 4% in-hospital mortality rate. Conclusions. Several key areas in both the database and aspects of patient care needing improvement have been highlighted. The implementation of similar databases has led to improved hip fracture care in other countries and we believe this can be replicated in Ireland. Prasad Ellanti, Breda Cushen, Adam Galbraith, Louise Brent, Conor Hurson, and Emer Ahern Copyright © 2014 Prasad Ellanti et al. All rights reserved. Changes in Dickkopf-1 (DKK1) and Sclerostin following a Loading Dose of Vitamin D2 (300,000 IU) Mon, 24 Nov 2014 13:46:25 +0000 Background. Vitamin D is important for bone health, although high loading doses have been associated with an increase in fracture risk. The mechanisms remain uncertain. Aim. We hypothesize that supraphysiological concentrations of 1,25 (OH)2 vitamin D may inhibit formation by increasing the production of Wnt inhibitors: sclerostin and DKK1. Subjects and Methods. We measured serum sclerostin and DKK1 in 34 patients (21 F, 13 M) aged mean (SD) 61.3 (15.6) years with vitamin D deficiency/insufficiency treated with a loading dose of vitamin D2 (300,000 IU) intramuscularly. Blood samples were taken at baseline and serially up to 3 months. Results. Serum 1,25 (OH)2 vitamin D increased markedly at 3 months (mean (SD) baseline 116 (63), 3 months : 229 (142) pmol/L, ). There was a significant correlation between sclerostin and DKK1 at baseline (, ) and at 3 months (, ). A significant inverse correlation was observed between sclerostin and eGFR at 3 months (, ). Sclerostin increased significantly at 3 months (). In a multilinear regression analysis with % change in sclerostin and DKK1 as dependent variable, a positive significant association was observed with % change in 1,25 (OH)2 vitamin D (), independent of changes in PTH and following correction for confounders such as age, gender, BMI, BMD and eGFR. Conclusions. Supraphysiological concentration in 1,25 (OH)2 vitamin D achieved following a loading dose of vitamin D increases sclerostin and may inhibit Wnt signalling. This may have detrimental effects on bone. A. Sankaralingam, R. Roplekar, C. Turner, R. N. Dalton, and G. Hampson Copyright © 2014 A. Sankaralingam et al. All rights reserved. Bone Mineral Density in Gravida: Effect of Pregnancies and Breast-Feeding in Women of Differing Ages and Parity Thu, 20 Nov 2014 09:25:09 +0000 Changes of bone during pregnancy and during lactation evaluated by bone mineral density (BMD) may have implications for risk of osteoporosis and fractures. We studied BMD in women of differing ages, parity, and lactation histories immediately postpartum for BMD, -scores, and -scores. Institutional Review Board approval was received. All women while still in hospital postpartum were asked to participate. BMD was performed by dual-energy X-ray absorptiometry (DXA) machine at femoral neck (FN) and lumbar spine (LS) by a single technician. Of 132 participants, 73 (55.3%) were ≤30 years; 27 (20.5%) were primiparous; 36 (27.3%) were grand multiparous; 35 (26.5%) never breast fed. Mean FN -scores and -scores were higher than respective mean LS scores, but all means were within the normal limits. Mean LS -scores and -scores were highest in the grand multiparas. There were only 2 (1.5%) outliers with low -scores. We conclude that, in a large cohort of Israeli women with BMD parameters assessed by DXA within two days postpartum, mean -scores and -scores at both the LS and FN were within normal limits regardless of age (20–46 years), parity (1–13 viable births), and history of either no or prolonged months of lactation (up to 11.25 years). Ehud Lebel, Yuri Mishukov, Liana Babchenko, Arnon Samueloff, Ari Zimran, and Deborah Elstein Copyright © 2014 Ehud Lebel et al. All rights reserved. Osteoporosis in Healthy South Indian Males and the Influence of Life Style Factors and Vitamin D Status on Bone Mineral Density Tue, 11 Nov 2014 08:58:57 +0000 Objective. To study the prevalence of osteoporosis and vitamin D deficiency in healthy men and to explore the influence of various life style factors on bone mineral density (BMD) and also to look at number of subjects warranting treatment. Methods. Ambulatory south Indian men aged above 50 were recruited by cluster random sampling. The physical activity, risk factors in the FRAX tool, BMD, vitamin D, and PTH were assessed. The number of people needing treatment was calculated, which included subjects with osteoporosis and osteopenia with 10-year probability of major osteoporotic fracture >20 percent and hip fracture >3 percent in FRAX India. Results. A total of 252 men with a mean age of 58 years were studied. The prevalence of osteoporosis and osteopenia at any one site was 20% (50/252) and 58%, respectively. Vitamin D deficiency (<20 ng/dL) was seen in 53%. On multiple logistic regression, BMI (OR 0.3; value = 0.04) and physical activity (OR 0.4; value < 0.001) had protective effect on BMD. Twenty-five percent warranted treatment. Conclusions. A significantly large proportion of south Indian men had osteoporosis and vitamin D deficiency. Further interventional studies are needed to look at reduction in end points like fractures in these subjects. Sahana Shetty, Nitin Kapoor, Dukhabandhu Naik, Hesarghatta Shyamasunder Asha, Suresh Prabu, Nihal Thomas, Mandalam Subramaniam Seshadri, and Thomas Vizhalil Paul Copyright © 2014 Sahana Shetty et al. All rights reserved. The Therapeutic Effectiveness of the Coadministration of Weekly Risedronate and Proton Pump Inhibitor in Osteoporosis Treatment Sun, 09 Nov 2014 09:47:25 +0000 This trial was conducted to investigate the long-term effects of proton pump inhibitor (PPI) coadministration on the efficacy of weekly risedronate treatment for osteoporosis. Ninety-six women over 50 years old with low bone mineral density (BMD) participated in this trial. Subjects were randomly divided into 2 groups: a 17.5 mg dose of sodium risedronate was administered weekly, with or without a daily 10 mg dose of sodium rabeprazole ( and 47 in the BP + PPI and BP groups, resp.). The following biomarkers were measured at the baseline and every 3 months: bone-specific alkaline phosphatase, N-terminal telopeptide of type I collagen corrected for creatinine, parathyroid hormone, BMD of the lumbar spine, and physical parameters evaluated according to the SF-36v2 Health Survey. Statistical comparisons of these parameters were performed after 6, 12, 18, and 24 months. The Δ values of improvement in physical functioning after 12 months and bodily pain after 6 and 12 months in the BP + PPI group were significantly larger than those in the BP group. These results suggest that PPI does not adversely affect bone metabolism. Alternatively, approved bone formation by concomitant PPI treatment may have had favorable effects on the improvement of bodily pain and physical functions. Mizue Tanaka, Soichiro Itoh, Taro Yoshioka, and Kimihiro Yamashita Copyright © 2014 Mizue Tanaka et al. All rights reserved. Differences in In Vitro Disintegration Time among Canadian Brand and Generic Bisphosphonates Thu, 02 Oct 2014 11:41:46 +0000 The objective of this study was to compare the disintegration times among Canadian-marketed brand (alendronate 70 mg, alendronate 70 mg plus vitamin D 5600 IU, and risedronate 35 mg) and generic (Novo-alendronate 70 mg and Apo-alendronate 70 mg) once-weekly dosed bisphosphonates. All disintegration tests were performed with a Vanderkamp Disintegration Tester. Disintegration was deemed to have occurred when no residue of the tablet, except fragments of insoluble coating or capsule shell, was visible. Eighteen to 20 samples were tested for each bisphosphonate group. The mean (±standard deviation) disintegration times were significantly faster for Apo-alendronate ( seconds) and Novo-alendronate ( seconds) as compared to brand alendronate ( seconds), brand alendronate plus vitamin D ( seconds), or brand risedronate ( seconds). The significantly faster disintegration of the generic tablets as compared to the brand bisphosphonates may have concerning safety and effectiveness implications for patients administering these therapies. Wojciech P. Olszynski, Jonathan D. Adachi, and K. Shawn Davison Copyright © 2014 Wojciech P. Olszynski et al. All rights reserved. Comorbidity and Healthcare Expenditure in Women with Osteoporosis Living in the Basque Country (Spain) Wed, 01 Oct 2014 13:10:59 +0000 Objectives. This study aimed to establish the prevalence of multimorbidity in women diagnosed with osteoporosis and to report it by deprivation index. The characteristics of comorbidity in osteoporotic women are compared to the general female chronic population, and the impact on healthcare expenditure of this population group is estimated. Methods. A cross-sectional analysis that included all Basque Country women aged 45 years and over ( = 579,575) was performed. Sociodemographic, diagnostic, and healthcare cost data were extracted from electronic databases for a one-year period. Chronic conditions were identified from their diagnoses and prescriptions. The existence of two or more chronic diseases out of a list of 47 was defined as multimorbidity. Results. 9.12% of women presented osteoporosis and 85.04% of them were multimorbid. Although multimorbidity in osteoporosis increased with age and deprivation level, prevalence was higher in the better-off groups. Women with osteoporosis had greater risk of having other musculoskeletal disorders but less risk of having diabetes (RR = 0.65) than chronic patients without osteoporosis. People with poorer socioeconomic status had higher healthcare cost. Conclusions. Most women with osteoporosis have multimorbidity. The variety of conditions emphasises the complexity of clinical management in this group and the importance of maintaining a generalist and multidisciplinary approach to their clinical care. Roberto Nuño-Solinis, Carolina Rodríguez-Pereira, Edurne Alonso-Morán, and Juan F. Orueta Copyright © 2014 Roberto Nuño-Solinis et al. All rights reserved.