The determinants of fracture in men

Osteoporosis represents an increasingly important clinical and public health problem among older men. Estimates indicated that 1-2 million (3-6%) men aged 50 years and over in the United States have osteoporosis and 8-13 million (28- 47%) have osteopenia. The lifetime risk of suffering a hip, spine or forearm fracture for a 50-year-old man is 13%, similar to the risk for prostate cancer. The number of osteoporotic fractures in men is expected to increase dramatically due to aging of the population and secular increases in fracture rates. Identification of men who are at greatest risk of osteoporosis and the risk factors, which predispose men to fracture, are essential so that preventive steps can be taken. Data on risk factors are emerging but many questions remain. Men may fracture at a higher bone mineral density (BMD) level than women. However, estimates of volumetric BMD, which correct in part for gender differences in bone size, and risk of fracture, may actually show similar relationships in men and women. Fracture rates are similar in older African American women and Caucasian men. Improved understanding of ethnic differences in fracture could identify potential reasons for gender differences. Family history and genetic factors are also important risk factors for fractures but the specific candidate genes are not known and whether gender modifies the effects of these genetic polymorphisms on BMD and the risk of fracture is also not known. In general, lifestyle factors and anthropometric measurements show similar relationships with fractures in men and women although few comprehensive prospective studies have been conducted. Current data will be reviewed on the relationships between markers of skeletal health, genetic polymorphisms, lifestyle and anthropometric factors and fracture.     

The prevention and treatment of osteoporosis: a review

Osteoporosis is a disorder characterized by reduced bone strength, diminished bone density, and altered macrogeometry and microscopic architecture. Adult bone mass is the integral measurement of the bone mass level achieved at the peak minus the rate and duration of subsequent bone loss. There is clearly a genetic predisposition to attained peak bone mass, which occurs by a person's mid-20s. Bone loss with age and menopause are universal, but rates vary among individuals. Both peak bone mass and subsequent bone loss can be modified by environmental factors, such as nutrition, physical activity, and concomitant diseases and medications. Osteoporosis prevention requires adequate calcium and vitamin D intake, regular physical activity, and avoiding smoking and excessive alcohol ingestion. Risk of fracture determines whether medication is also warranted. A previous vertebral or hip fracture is the most important predictor of fracture risk. Bone density is the best predictor of fracture risk for those without prior adult fractures. Age, weight, certain medications, and family history also help establish a person's risk for osteoporotic fractures. All women should have a bone density test by the age of 65 or younger (at the time of menopause) if risk factors are present. Guidelines for men are currently in development. Medications include both antiresorptive and anabolic types. Antiresorptive medications--estrogens, selective estrogen receptor modulators (raloxifene), bisphosphonates (alendronate, risedronate, and ibandronate) and calcitonins--work by reducing rates of bone remodeling. Teriparatide (parathyroid hormone) is the only anabolic agent currently approved for osteoporosis in the United States. It stimulates new bone formation, repairing architectural defects and improving bone density. All persons who have had osteoporotic vertebral or hip fractures and those with a bone mineral density diagnostic of osteoporosis should receive treatment. In those with a bone mineral density above the osteoporosis range, treatment may be indicated depending on the number and severity of other risk factors.     

Management of osteoporosis

Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5 million fragility fractures per year. The consequences of these fractures include pain, disability, depression, loss of independence, and increased mortality. The burden to the healthcare system, in terms of cost and resources, is tremendous, with an estimated direct annual USA healthcare expenditure of about $17 billion. With longer life expectancy and the aging of the baby-boomer generation, the number of men and women with osteoporosis or low bone density is expected to rise to over 61 million by 2020. Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. Any fragility fracture greatly increases the risk of future fractures. Most patients with osteoporosis are not being diagnosed or treated. Even those with previous fractures, who are at extremely high risk of future fractures, are often not being treated. It is preferable to diagnose osteoporosis by bone density testing of high risk individuals before the first fracture occurs. If osteoporosis or low bone density is identified, evaluation for contributing factors should be considered. Patients on long-term glucocorticoid therapy are at especially high risk for developing osteoporosis, and may sustain fractures at a lower bone density than those not taking glucocorticoids. All patients should be counseled on the importance of regular weight-bearing exercise and adequate daily intake of calcium and vitamin D. Exposure to medications that cause drowsiness or hypotension should be minimized. Non-pharmacologic therapy to reduce the non-skeletal risk factors for fracture should be considered. These include fall prevention through balance training and muscle strengthening, removal of fall hazards at home, and wearing hip protectors if the risk of falling remains high. Pharmacologic therapy can stabilize or increase bone density in most patients, and reduce fracture risk by about 50%. By selecting high risk patients for bone density testing it is possible to diagnose this disease before the first fracture occurs, and initiate appropriate treatment to reduce the risk of future fractures.     

Clinical usefulness of bone mineral density and the health economy consequences of osteoporosis

Bone mineral density is one of the strongest risk factors for osteoporotic fractures and can be used, in combination with other risk factors, to identify groups at high risk of osteoporosis who could benefit from treatment to prevent fractures. Health economic studies have shown that the treatment of these high-risk patients is cost-effective.     

Bone Health History in Breast Cancer Patients on Aromatase Inhibitors

A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.     

Osteoporosis: the current status of mesenchymal stem cell-based therapy

Osteoporosis, or bone loss, is a progressive, systemic skeletal disease that affects millions of people worldwide. Osteoporosis is generally age related, and it is underdiagnosed because it remains asymptomatic for several years until the development of fractures that confine daily life activities, particularly in elderly people. Most patients with osteoporotic fractures become bedridden and are in a life-threatening state. The consequences of fracture can be devastating, leading to substantial morbidity and mortality of the patients. The normal physiologic process of bone remodeling involves a balance between bone resorption and bone formation during early adulthood. In osteoporosis, this process becomes imbalanced, resulting in gradual losses of bone mass and density due to enhanced bone resorption and/or inadequate bone formation. Several growth factors underlying age-related osteoporosis and their signaling pathways have been identified, such as osteoprotegerin (OPG)/receptor activator of nuclear factor B (RANK)/RANK ligand (RANKL), bone morphogenetic protein (BMP), wingless-type MMTV integration site family (Wnt) proteins and signaling through parathyroid hormone receptors. In addition, the pathogenesis of osteoporosis has been connected to genetics. The current treatment of osteoporosis predominantly consists of antiresorptive and anabolic agents; however, the serious adverse effects of using these drugs are of concern. Cell-based replacement therapy via the use of mesenchymal stem cells (MSCs) may become one of the strategies for osteoporosis treatment in the future.     

Atypical subtrochanteric femoral shaft fractures: role for mechanics and bone quality

Bisphosphonates are highly effective agents for reducing osteoporotic fractures in women and men, decreasing fracture incidence at the hip and spine up to 50%. In a small subset of patients, however, these agents have recently been associated with ''atypical femoral fractures'' (AFFs) in the subtrochanteric region or the diaphysis. These fractures have several atypical characteristics, including occurrence with minimal trauma; younger age than typical osteoporotic fractures; occurrence at cortical, rather than cancellous sites; early radiographic appearance similar to that of a stress fracture; transverse fracture pattern rather than the familiar spiral or transverse-oblique morphologies; initiation on the lateral cortex; and high risk of fracture on the contralateral side, at the same location as the initial fracture. Fracture is a mechanical phenomenon that occurs when the loads applied to a structure such as a long bone exceed its load-bearing capacity, either due to a single catastrophic overload (traumatic failure) or as a result of accumulated damage and crack propagation at sub-failure loads (fatigue failure). The association of AFFs with no or minimal trauma suggests a fatigue-based mechanism that depends on cortical cross-sectional geometry and tissue material properties. In the case of AFFs, bisphosphonate treatment may alter cortical tissue properties, as these agents are known to alter bone remodeling. This review discusses the use of bisphosphonates, their effects on bone remodeling, mechanics and tissue composition, their significance as an effective therapy for osteoporosis, and why these agents may increase fracture risk in a small population of patients.     

Relevance of osteoporosis in women with fracture of the femoral neck.

A prospective study of fractures of the femoral neck was conducted over 12 months in order to ascertain the relevance of generalised osteoporosis as determined by metacarpal morphometry. A series of some 200 women sustaining a fracture of the femoral neck after minor trauma had bone mass measurements similar to those of a control population of normal women, and 16% were not osteoporotic. A history of previous fractures was documented in one third of the women, but this was unrelated to the presence or severity of osteoporosis, although over half of the fractures had occurred within the previous four years. Trochanteric fractures were seen more commonly in severely osteoporotic women (p less than 0.005), whereas cervical fractures predominated in those who were not osteoporotic. These findings support the hypothesis that postural instability is the major determinant for femoral neck fracture and that generalised osteoporosis, rather than being a prerequisite for fracture, merely determines the type of fracture sustained.     

PKP治疗骨质疏松性椎体压缩骨折的预后评价及继发危险因素分析

目的:分析椎弓根入路行椎体后凸成形术(PKP)治疗骨质疏松性椎体压缩骨折的预后评价及继发危险因素分析。方法:选择2016年2月-2018年2月我院收治的骨质疏松性椎体压缩骨折患者85例纳入本次研究,采用随机数表法分为观察组(n=43)和对照组(n=42)。对照组使用经皮椎体成形术进行治疗,观察组采用PKP进行治疗。比较两组患者手术情况、术后情况、椎体前缘高度丢失率、Cobb角、继发性骨折发生情况及分析骨质疏松性椎体压缩骨折患者术后继发骨折的危险因素。结果:观察组手术时间、透视次数、骨水泥注入量、术中出血量均显著低于对照组,差异显著(P0.05);观察组疼痛缓解时间、下地时间及住院时间均显著低于对照组,差异显著(P0.05);治疗前,两组椎体前缘高度丢失率、Cobb角比较,无显著差异;治疗后,两组患者的椎体高度丢失率明显下降,但两组术后7 d、术后6月两组椎体前缘高度丢失率、Cobb角比较无显著差异;观察组术后12月椎体前缘高度丢失率、Cobb角低于对照组,差异显著(P0.05);所有患者均随访12月,其中22例(25.88%)发生继发性椎体骨折,进行单因素分析,结果发现,两组患者性别、骨折部位、局部矢状面后凸角度、骨水泥量、椎体高度恢复、术后抗骨质疏松治疗差异无统计学意义(P0.05);骨质疏松原因、骨水泥椎间隙渗漏、术后支具佩戴、原发骨折类型与骨质疏松性椎体压缩骨折患者术后发生继发骨折相关(P0.05)。多因素Logistic分析显示,骨质疏松原因、骨水泥椎间隙渗漏、术后支具佩戴、原发骨折类型均是骨质疏松性椎体压缩骨折患者术后发生继发骨折的独立危险因素(P0.05)。结论:在骨质疏松性椎体压缩骨折患者中应用PKP可有效改善手术情况,随着时间的延长,PKP更有利于维持患者椎体高度;骨质疏松原因、骨水泥椎间隙渗漏、术后支具佩戴、原发骨折类型是骨质疏松性椎体压缩骨折患者术后发生继发骨折的危险因素,临床上对于具有危险因素的患者引起重视,并采取干预措施。     

Stéroides sexuels et ostéoporose chez l'homme

Several epidemiological studies have shown that about 25 per cent of hip fractures and 20 per cent of symptomatic vertebral fractures occur in men. The lifetime risk of hip fracture was estimated to be about 6 to 8 per cent and the risk of any osteoporotic fracture was estimated to be about 18 per cent in 50-year-old white men. In about 60% of cases in men, bone loss is secondary to several pathological conditions, such as long-term steroid therapy, severe hypogonadism, smoking or alcohol abuse or gastrointestinal disorders. In 40% of cases, osteoporosis is primary or idiopathic in men between the ages of 40 and 60 years. Genetic factors, a defect of boneforming cells or abnormal serum levels of bioavailable sex steroids could explain bone loss and fragility fractures in these men. It has been shown that hypogonadism is associated with a marked increase in bone remodelling and particularly in bone resorption with a dramatic loss in trabecular bone. It is now known that testosterone is partly transformed into estradiol by aromatase. Testosterone may therefore act on bone in two ways: it directly stimulates bone formation and estradiol regulates bone remodelling and inhibits bone resorption. Finally, in men over the age of 60 without hypogonadism, it has been shown that bone mineral density and fracture risk were better correlated with serum levels of bioavailable estradiol and Sex Hormone Binding Globulin than with serum testosterone levels.     

Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk

Osteoporosis, a key predictor of hip fractures can be treated using a variety of safe and effective interventions. Nevertheless, optimally effective strategies for the prevention of hip fractures must also incorporate efforts to address a broad range of other potentially reversible factors. Hyperthyroidism, anticonvulsants, caffeine and smoking may decrease bone mass and increase fracture risk at any age. In older individuals it is important to also consider additional risk factors, including long-acting benzodiazepines, poor vision and sarcopenia. The presence of sarcopenia, an age-related decline in muscle bulk and quality enhances the risk of frailty and possibly also hip fracture, particularly if associated with diminished functional mobility, lower quadriceps strength and poor balance or body sway. In this review we examine evidence which indicates the presence of endocrine-immune dysregulation in both osteoporosis and sarcopenia. Post-menopausal declines in serum estrogen and androgen levels contribute to increases in local bone levels of cytoclastic cytokines, followed by increased osteoclastogenesis and bone loss. Similarly, the presence of decreased gonadal hormones and IGF-1, combined with unusually high peripheral levels of cytokines, inflammatory mediators and coagulation markers all enhance the risk of sarcopenia and frailty. We propose that a translational research approach which emphasizes common pathophysiologic mechanisms in osteoporosis and sarcopenia could accelerate the speed of discovery of effective strategies for both frailty and hip fracture prevention.     

Osteoporosis Treatment After Osteoporotic Fractures: Data From a Single Medical Center

ObjectiveMost patients do not receive osteoporosis treatment after osteoporotic fracture. This study reviewed osteoporosis treatment after osteoporotic fractures in a center without a Fracture Liaison Service.MethodsWe identified all patients with hip, vertebral, humeral or radial fractures, evaluated in Meir Medical Center, in 2017. The exclusion criteria were not a Clalit Health Services member, high-energy fracture or 30-day postoperative mortality. The primary endpoint was osteoporosis drugs issued within 12 months of fracture. Secondary endpoints included bone densitometry and 1-year mortality.ResultsFive-hundred-eighty-two patients (average age 78.6 ± 11.1 years, 75.8% women) were included. There were 321 (55.5%) hip, 84 (14.1%) humeral, 33 (5.6%) vertebral, and 144 (24.7%) radial fractures. Osteoporosis drugs were issued to 26.5% of the patients; those with humeral fractures received the least (21.4%) and vertebral, the most (30.3%; P = .51). Bone densitometry was performed in 23.2% of patients. One-year mortality after hip fracture was 12.1%, followed by humeral (3.6%; P < .05). Logistic regression showed that previous treatment (odds ratio [OR] = 7.4; 95% confidence interval [CI] 3.6–15.2), bone densitometry (OR = 4.4; 95% CI 2.6–7.4) and endocrinology visit (OR = 2.6; 95% CI, 1.4–4.6) were the most important factors associated with treatment.ConclusionFewer than one third of patients received pharmacotherapy within 1 year after fracture. Because pharmacotherapy reduces future fractures and mortality, we recommend that medical staff who care for patients with fracture adopt practical and effective strategies to increase treatment rates among patients with osteoporotic fractures.     

Prediction of osteoporotic fractures by postural instability and bone density.

OBJECTIVE--To investigate the utility of risk factors such as bone mineral density, lifestyle, and postural stability in the prediction of osteoporotic fractures. DESIGN--Longitudinal, epidemiological, and population based survey. SETTING--City of Dubbo, New South Wales. SUBJECTS--All residents of Dubbo aged > or = 60 on 1 January 1989. MAIN OUTCOME MEASURE--Incidence of fracture for individual subjects. RESULTS--The overall incidence of atraumatic fractures in men and women was 1.9% and 3.1% per annum respectively. The predominant sites of fracture were hip (18.9%), distal radius (18.5%), ribs and humerus (11.9% in each case), and ankle and foot (9.1% and 6.6% respectively). Major predictors of fractures in men and women were femoral neck bone mineral density, body sway, and quadriceps strength. Age, years since menopause, height, weight, and lifestyle factors were also correlated with bone mineral density and body sway and hence were indirect risk factors for fracture. Discriminant function analysis correctly identified 96% and 93% (sensitivities 88% and 81%) of men and women, respectively, who subsequently developed atraumatic fractures. Predictions based on this model indicated that a woman with a bone mineral density in the lowest quartile in the hip together with high body sway had a 8.4% probability of fracture per annum. This represented an almost 14-fold increase in risk of fracture compared with a woman in the highest bone mineral density quartile with low postural sway. An individual with all three predictors in the "highest risk" quartile had a 13.1% risk of fracture per annum. CONCLUSIONS--Bone mineral density, body sway, and muscle strength are independent and powerful synergistic predictors of fracture incidence.     

Recommendations on the management of fragility fracture risk in women younger than 70 years

The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for fracture. There are precise diagnostic methods, including a tool to diagnose the risk for fracture. Yet there continues to be an under-diagnosis, with the unrecoverable delay in instituting preventive measures. Women under the age of 70 years, being much more numerous than those older, and having risk factors, are a group in which it is essential to avoid that first fragility fracture. Today it is usual not to differentiate between the treatment and the prevention of osteoporosis since the common aim is to prevent fragility fractures. Included in this are women with osteoporosis or with low bone mass and increased risk for fracture, for whom risk factors play a primary role. There is clearly controversy over the type of treatment and its duration, especially given the possible adverse effects of long-term use. This justifies the concept of sequential treatment, even more so in women under the age of 70, since they presumably will need treatment for many years. Bone metabolism is age-dependent. In postmenopausal women under 70 years of age, the increase in bone resorption is clearly predominant, related to a sharp drop in estrogens. Thus a logical treatment is the prevention of fragility fractures by hormone replacement therapy (HRT) and, in asymptomatic women, selective estradiol receptor modulators (SERMs). Afterwards, there is a period of greater resorption, albeit less intense but continuous, when one could utilise anti-resorptive treatments such as bisphosphonates or denosumab or a dual agent like strontium ranelate. Bone formation treatment, such as parathyroid hormone (PTH), in women under 70 years will be uncommon. That is because it should be used in cases where the formation is greatly diminished and there is a high risk for fracture, something found in much older women.     

Contribution of bone mineral density and bone turnover markers to the estimation of risk of osteoporotic fracture in postmenopausal women

In osteoporosis, the main cause for concern is the increase in the risk of fractures. The level of bone mineral density (BMD) measured by various techniques has been shown to be a strong predictor of fracture risk in postmenopausal women. However, half of patients with incident fractures have BMD value above the diagnostic threshold of osteoporosis defined as a T-score of -2.5 SD or more below the average value of young healthy women. Clearly there is a need for improvement in the identification of patients at risk for fracture. Several prospective studies have shown that an increased bone resorption evaluated by specific biochemical markers was associated with increased risk of the hip, spine and non-vertebral fractures independently of BMD. The use of bone markers in individual patients may be appropriate in some situations, especially in women who are not detected at risk by BMD measurements. For example, in the OFELY study including 668 postmenopausal women followed prospectively over 9 years, we found that among the 115 incident fractures, 54 (47%) actually occurred in non-osteoporotic women. Among these women, the combination of bone markers and history of previous fracture was highly predictive of fracture risk. Thus, bone markers may be used in the assessment of fracture risk in selected cases in which BMD and clinical risk factors are not enough to take a treatment decision. Advances in our knowledge of bone matrix biochemistry, most notably of post-translational modifications in type I collagen, may allow identification of biochemical markers that reflect changes in the material property of bone, which is an important determinant of bone strength. Preliminary in vitro studies indicate that the extent of post-translational modifications of collagen--which can be reflected in vivo by the measurement of the urinary ratio between native and isomerised type I collagen--play a role in determining the mechanical competence of cortical bone, independently of BMD. Further studies in osteoporosis should explore the changes in these biochemical parameters of bone matrix as they may represent a key component of bone quality.     

Clinical Significance and Pathogenesis of Osteoporosis

The development of osteoporosis with advancing age in man is a widespread if not a universal phenomenon. The average loss between youth and old age amounts to about 15% of the skeleton but involves a much larger proportion of trabecular than of cortical bone.The principal clinical manifestation of osteoporosis is fracture, and three osteoporotic fracture syndromes can be defined: the lower forearm fracture, which predominantly affects women between the ages of 50 and 65; the fracture of the proximal femur, which affects both sexes over the age of 70; and the relatively rare vertebral crush fracture syndrome, which may present at any age but is most common in elderly women.The lower forearm fracture rate is inversely related to the mean normal lower forearm x-ray “density” of the wrist, which falls by about 30% in the 15 years following the menopause. This process, which is associated with corresponding trabecular bone loss elsewhere in the skeleton, is associated with a corresponding rise in the fasting urinary calcium excretion. Some degree of negative calcium balance, and consequent bone resorption, probably occurs in everyone during the later part of the night because calcium absorption is completed within about three to five hours of a meal. In postmenopausal women, however, the sensitivity of the bone to parathyroid hormone appears to be increased, and their nocturnal negative calcium balance therefore comes to exceed the positive balance which can be achieved during the waking hours.Femoral neck fractures in old people reflect the further progression of osteoporosis with advancing age since the fracture rate is inversely correlated with the mean thickness of the metacarpal cortex in the normal population. This progressive osteoporosis is associated with and could well result from a steady decline in calcium absorption which is at least partially attributable to vitamin-D deficiency and reversible on vitamin-D treatment.The vertebral crush fracture syndrome represents a severe degree of spinal osteoporosis which may be associated with relatively normal peripheral bones. It probably results from an accelerated negative calcium balance which mobilizes trabecular bone preferentially. Some of the factors which may contribute to this accelerated negative balance have been identified and include a reduced rate of bone turnover, impaired calcium absorption, and low oestrogen activity as judged by vaginal smears, but there may well be others as yet unidentified.     

The prospective evaluation of the osteoporotic vertebral fractures incidence in a random population sample

Introduction Osteoporotic vertebral fractures are mostly incidental but in some patients may lead to clinical symptoms, characteristic deformations of the vertebral column and increase total mortality. The aim of the study was to evaluate the prevalence of osteoporotic vertebral fractures and risk factors for osteoporosis in a random sample of Szczecin inhabitants aged over 50 in the relation to the whole European population examined in the frame of EVOS (European Vertebral Osteoporosis Study) and its prospective phase - EPOS (European Prospective Osteoporosis Study). At the baseline, 607 persons were studied, including 301 women and 306 men. Material and methods The questionnaire on the risk factors for osteoporosis and the spine X-rays analysed by morphometry, were taken in all subjects. The incidence of osteoporotic vertebral deformity in the studied population was similar in both sexes (12.6% women and 10,3% men) but in men aged 50-64 fracture incidence was significantly higher in comparison with women. The prevalence of new vertebral fractures examined after 4 years was higher in women than in men (9.1 vs 6.4/1000 persons years). Among the risk factors for osteoporosis, low physical activity and prolonged immobilization in women significantly influenced the incidence of vertebral deformities. Conclusions: 1) The study shows the high incidence of risk factors and osteoporotic vertebral deformities in the population of Szczecin inhabitants aged over 50. 2) Visual assessment only with a combination with morphometry is an optimal tool for detection of incident vertebral fractures.     

In-Vivo Assessment of Femoral Bone Strength Using Finite Element Analysis (FEA) Based on Routine MDCT Imaging: A Preliminary Study on Patients with Vertebral Fractures

PurposeTo experimentally validate a non-linear finite element analysis (FEA) modeling approach assessing in-vitro fracture risk at the proximal femur and to transfer the method to standard in-vivo multi-detector computed tomography (MDCT) data of the hip aiming to predict additional hip fracture risk in subjects with and without osteoporosis associated vertebral fractures using bone mineral density (BMD) measurements as gold standard.MethodsOne fresh-frozen human femur specimen was mechanically tested and fractured simulating stance and clinically relevant fall loading configurations to the hip. After experimental in-vitro validation, the FEA simulation protocol was transferred to standard contrast-enhanced in-vivo MDCT images to calculate individual hip fracture risk each for 4 subjects with and without a history of osteoporotic vertebral fractures matched by age and gender. In addition, FEA based risk factor calculations were compared to manual femoral BMD measurements of all subjects.ResultsIn-vitro simulations showed good correlation with the experimentally measured strains both in stance (R² = 0.963) and fall configuration (R² = 0.976). The simulated maximum stress overestimated the experimental failure load (4743 N) by 14.7% (5440 N) while the simulated maximum strain overestimated by 4.7% (4968 N). The simulated failed elements coincided precisely with the experimentally determined fracture locations. BMD measurements in subjects with a history of osteoporotic vertebral fractures did not differ significantly from subjects without fragility fractures (femoral head: p = 0.989; femoral neck: p = 0.366), but showed higher FEA based risk factors for additional incident hip fractures (p = 0.028).ConclusionFEA simulations were successfully validated by elastic and destructive in-vitro experiments. In the subsequent in-vivo analyses, MDCT based FEA based risk factor differences for additional hip fractures were not mirrored by according BMD measurements. Our data suggests, that MDCT derived FEA models may assess bone strength more accurately than BMD measurements alone, providing a valuable in-vivo fracture risk assessment tool.     

Night shift work and osteoporosis: evidence and hypothesis

Osteoporosis is an important public health problem worldwide. Among the countries with a very high population risk of fractures, there are those with the highest level of economic development. Osteoporotic fractures are the main cause of disability among elderly people, and the resultant disabilities require particularly large financial support associated not only with the direct treatment of the fracture but also with the necessity for long-term rehabilitation and care for the disabled person. Many well-established factors can have impact on bone mass and fracture risk. Recently, it has been hypothesized that working during nighttime which leads to endocrine disorders may have an indirect impact on bone physiology among night shift workers. Therefore, it can be presumed that the night shift work may contribute to the etiology of osteoporosis. The aim of our work was to make a review of the epidemiological evidence on the association between night shift work and bone mineral density or fracture risk as well as to discuss the potential biological mechanisms linking the work under this system with the development of osteoporosis. We have identified only four studies investigating the association between system of work and bone mineral density or fracture risk among workers. The findings of three out of four studies support the hypothesis. None of the studies has investigated a potential relationship between night shift work and bone turnover markers. Given that there have been no epidemiological studies in European countries that would concern working populations and the noticeable difference in the risk of osteoporosis between communities, further studies are warranted to elucidate the problem. It is presumed that further in-depth studies will not only identify the underlying factors of the disease but also contribute to developing guidelines for policy makers and employers for primary prevention of osteoporosis in workplace.     

Genetics of osteoporosis from genome-wide association studies: advances and challenges

Osteoporosis is among the most common and costly diseases and is increasing in prevalence owing to the ageing of our global population. Clinically defined largely through bone mineral density, osteoporosis and osteoporotic fractures have reasonably high heritabilities, prompting much effort to identify the genetic determinants of this disease. Genome-wide association studies have recently provided rapid insights into the allelic architecture of this condition, identifying 62 genome-wide-significant loci. Here, we review how these new loci provide an opportunity to explore how the genetics of osteoporosis can elucidate its pathophysiology, provide drug targets and allow for prediction of future fracture risk.