Osteoporosis : the emperor has no clothes

Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. PathophysiologyMost fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. ScreeningCurrently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. TreatmentThe evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65-80years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20-25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment.Peer reviewe

Revision rates after primary hip and knee replacement in England between 2003 and 2006

<b>Background</b>: Hip and knee replacement are some of the most frequently performed surgical procedures in the world. Resurfacing of the hip and unicondylar knee replacement are increasingly being used. There is relatively little evidence on their performance. To study performance of joint replacement in England, we investigated revision rates in the first 3 y after hip or knee replacement according to prosthesis type. <b>Methods and Findings</b>: We linked records of the National Joint Registry for England and Wales and the Hospital Episode Statistics for patients with a primary hip or knee replacement in the National Health Service in England between April 2003 and September 2006. Hospital Episode Statistics records of succeeding admissions were used to identify revisions for any reason. 76,576 patients with a primary hip replacement and 80,697 with a primary knee replacement were included (51% of all primary hip and knee replacements done in the English National Health Service). In hip patients, 3-y revision rates were 0.9% (95% confidence interval [CI] 0.8%–1.1%) with cemented, 2.0% (1.7%–2.3%) with cementless, 1.5% (1.1%–2.0% CI) with “hybrid” prostheses, and 2.6% (2.1%–3.1%) with hip resurfacing (p < 0.0001). Revision rates after hip resurfacing were increased especially in women. In knee patients, 3-y revision rates were 1.4% (1.2%–1.5% CI) with cemented, 1.5% (1.1%–2.1% CI) with cementless, and 2.8% (1.8%–4.5% CI) with unicondylar prostheses (p < 0.0001). Revision rates after knee replacement strongly decreased with age. <b>Interpretation</b>: Overall, about one in 75 patients needed a revision of their prosthesis within 3 y. On the basis of our data, consideration should be given to using hip resurfacing only in male patients and unicondylar knee replacement only in elderly patients

Motives for physical activity in older men and women: A twin study using accelerometer-measured physical activity

Motives for physical activity may vary considerably by age, sex, and the level of physical activity. We aimed to examine motives for physical activity in older men and women with different physical activity levels as well as whether genetic and/or environmental factors explain those motives. Finnish twins (mean age 72.9 years, 262 full twin pairs) self-reported their motives for physical activity. Time spent on moderate-to-vigorous physical activity was monitored using a hip-worn accelerometer. Comparisons between the different physical activity groups of older twins (n = 764-791/motive dimension) were analyzed using the Wald test, and effect sizes were calculated as Cohen's d. Quantitative genetic modeling was used to estimate genetic and environmental contributions. For both sexes, the most frequently reported motives for physical activity were physical fitness, health maintenance, and psychological well-being. Conforming to others' expectations was more important for men than for women (P < .001, Cohen's d = 0.38), while appearance (P = .001 Cohen's d = -0.24) and psychological well-being (P = .02, Cohen's d = -0.17) were highlighted by women. Most of the motive dimensions differed significantly between the physically active and inactive individuals. It was estimated that 5%-42% of the variation in motives was contributed by genetic factors and 58%-95% by environmental factors. The result that environmental factors contribute in a great deal to motives indicates that interventions to motivate physically inactive older individuals to be physically active can be successful. However, personalized interventions are needed because sex and the level of physical activity were found to be associated with older individuals' motives for physical activity

Does Bone Resorption Stimulate Periosteal Expansion? A Cross-Sectional Analysis of b-C-telopeptides of Type I Collagen ( CTX),Genetic Markers of the RANKL Pathway, and Periosteal Circumference as Measured by

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Phosphate Binding with Sevelamer Preserves Mechanical Competence of Bone Despite Acidosis in Advanced Experimental Renal Insufficiency

Introduction Phosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI. Methods Forty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography). Results Sevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p Conclusions In this model of stage 3-4 CRI, sevelamer-HCl treatment ameliorated the decreases in femoral midshaft and neck mineral density, and restored bone strength despite prevailing acidosis. Therefore, treatment with sevelamer can efficiently preserve mechanical competence of bone in CRI.Peer reviewe

Temporal Trends in Vertebral Size and Shape from Medieval to Modern-Day

Human lumbar vertebrae support the weight of the upper body. Loads lifted and carried by the upper extremities cause significant loading stress to the vertebral bodies. It is well established that trauma-induced vertebral fractures are common especially among elderly people. The aim of this study was to investigate the morphological factors that could have affected the prevalence of trauma-related vertebral fractures from medieval times to the present day. To determine if morphological differences existed in the size and shape of the vertebral body between medieval times and the present day, the vertebral body size and shape was measured from the 4th lumbar vertebra using magnetic resonance imaging (MRI) and standard osteometric calipers. The modern samples consisted of modern Finns and the medieval samples were from archaeological collections in Sweden and Britain. The results show that the shape and size of the 4th lumbar vertebra has changed significantly from medieval times in a way that markedly affects the biomechanical characteristics of the lumbar vertebral column. These changes may have influenced the incidence of trauma- induced spinal fractures in modern populations

Low appendicular muscle mass is correlated with femoral neck bone mineral density loss in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>After menopause, rapid bone mass loss occurs in response to hypoestrogenism. Several studies suggest that muscle mass and bone mineral density (BMD) are positively associated in postmenopausal women. Therefore, it may be assumed that postmenopausal low appendicular muscle mass (aMM) can increase BMD loss in a short period of time.</p> <p>Objective</p> <p>The purpose of this study was to assess relationship of aMM with femoral neck BMD in postmenopausal women.</p> <p>Methods</p> <p>Prospective, controlled clinical Trial including 64 women aged 45-70 years, who had not had their last menstruation for at least one year. Subjects were divided into two groups: low aMM (n = 32), and normal aMM (n-32). Femoral neck BMD and muscle mass were measured by DXA at baseline and after twelve months. Pairwise and independent t tests were used for data analysis.</p> <p>Results</p> <p>Baseline weight, BMI and muscle mass (total and appendicular) significantly differ between groups (p < 0.05). After twelve months, femoral neck BMD was significantly lower in the group with low aMM, whereas no significant difference was observed in the group with normal aMM (p < 0.05).</p> <p>Conclusion</p> <p>In postmenopausal women, low appendicular muscle mass is associated negatively with femoral neck BMD in a short period of time.</p

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal

Background: Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Methods. Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Results: Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI - mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI - mid shaft (ICC 0.99; CV% 3.2). Conclusions: The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2 nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures

Genetic Determinants of Trabecular and Cortical Volumetric Bone Mineral Densities and Bone Microstructure

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Sources of stakeholder salience in the responsible investment movement: why do investors sign the Principles for Responsible Investment?

Since its inception in 2006, the United Nations-backed Principles for Responsible Investment (PRI) have grown to over 1300 signatories representing over $45 trillion. This growth is not slowing down. In this paper, we argue that there is a set of attributes which make the PRI salient as a stakeholder and its claim to sign the six PRI important to institutional investors. We use Mitchell et al.’s (Acad Manag Rev 22:853–886, 1997) theoretical framework of stakeholder salience, as extended by Gifford (J Bus Eth 92:79–97, 2010). We use as evidence confidential data from the annual survey of signatories carried out by the PRI in a 5-year period between 2007 and 2011. The findings highlight pragmatic and organizational legitimacy, normative and utilitarian power, and management values as the attributes that contribute most to the salience of the PRI as a stakeholder