Vitamina D y fracturas en el anciano

Osteoporosis and the subsequent fractures caused by this are a source of morbidity and mortality in the elderly population. It is also often the start of the cascade that culminates in frailty and dependence. Vitamin D has a direct relationship with the appearance of osteoporosis and with the risk of fractures. Receptors of this vitamin have also recently been described in other organs and systems of the body that are associated with muscle strength, cancer and overall mortality. Deficiency of this vitamin in the elderly population in Spain is very prevalent, both in the community and the hospitalised elderly. The diagnosis and treatment are straightforward and cheap. Its efficacy in the prevention of osteoporosis and in the appearance of fractures is perfectly demonstrated. In this review, we will look at the physiology and actions of this vitamin, as well as the principal studies that have demonstrated its effectiveness in the elderly population.     

老年髋部骨折患者抗骨质疏松的治疗

髋部骨折往往与高发病率、死亡率以及沉重的经济负担相联系,也是再次骨折的一个主要危险因素。因此加强老年髋部骨折患者的抗骨质疏松治疗及预防再次骨折成为提高该类人群生活质量的必要和关键,其中均衡的营养、补充钙和维生素D是基础,及早进行抗骨质疏松药物治疗是关键,而消除骨质疏松的继发原因、治疗并存疾病、适当的锻炼及防止跌倒则是重要的补充。总之,加强老年骨质疏松的多学科综合管理能够获得很好的临床效果。本文就抗骨质疏松药物在老年髋部患者和那些具有跌倒高风险人群中的疗效予以综述,以期为老年骨质疏松的管理提供借鉴。     

Vitamin D in the aging musculoskeletal system: an authentic strength preserving hormone

Until recently, vitamin D was only considered as one of the calciotrophic hormones without major significance in other metabolic processes in the body. Several recent findings have demonstrated that vitamin D plays also a role as a factor for cell differentiation, function and survival. Two organs, muscle and bone, are significantly affected by the presence, or absence, of vitamin D. In bone, vitamin D stimulates bone turnover while protecting osteoblasts of dying by apoptosis whereas in muscle vitamin D maintains the function of type II fibers preserving muscle strength and preventing falls. Furthermore, two major changes associated to aging: osteoporosis and sarcopenia, have been also linked to the development of frailty in elderly patients. In both cases vitamin D plays an important role since the low levels of this vitamin seen in senior people may be associated to a deficit in bone formation and muscle function. In this review, the interaction between vitamin D and the musculoskeletal components of frailty are considered from the basic mechanisms to the potential therapeutic approach. We expect that these new considerations about the importance of vitamin D in the elderly will stimulate an innovative approach to the problem of falls and fractures which constitutes a significant burden to public health budgets worldwide.     

Behandeling van osteoporose bij ouderen: wat is de evidence?

Many older people, especially women, and their doctors still see osteoporosis as part of the natural course of ageing instead of as a preventable or treatable disorder. Height loss, hyperkyphosis, back pain, and fractures are accepted as consequences of ageing. The notion that it is too late to start treatment in a late stage of the disease forms another barrier to treatment. Although most studies of fracture reduction with medical treatment were not designed for the "geriatric" population, the average age of participants in most clinical trials was about 70 years. In all major studies patients also received calcium and vitamin D supplements. Nowadays, clinicians can choose from several effective treatments for the prevention of osteoporotic fractures in high-risk postmenopausal women. Data on the anti-fracture potential of calcium/vitamin D, raloxifene, bisphosphonates, strontium ralenate, and parathyroid hormone are now available. Bisphosphonates and strontium ralenate are good choices for first- or second-line treatment, while for the time being parathyroid hormone should only be used for the second-line treatment of osteoporosis in the elderly.     

The therapeutic effects of alfacalcidol on bone strength, muscle metabolism and prevention of falls and fractures

Established osteoporosis in older patients of both sexes is characterized by decoupled bone remodelling induced by sex hormone deficits and by somatopause, but also by lack of vitamin D and reduced synthesis of the D-Hormone (calcitriol; 1.25 (OH)2D) in the kidneys and bone, as well as from lack of receptors and/or receptor affinity for D-Hormone in the target organs. Parallel to the decreased bone strength a loss of muscle power occurs, together with an increase in balance disorders and an increasing risk of "intrinsic", nonsyncopal locomotoric falls. In alfacalcidol therapy, D-Hormone is provided to the body in circumvention of its own regulation, by means of which higher hormone concentrations can be achieved in the target tissues than by administration of plain vitamin D. In vitro and in vivo experiments have provided growing evidence that D-Hormone analogs tend to normalize PTH, lead to an increase in the number and activity of osteoblasts, reduce the activity of osteoclasts, and might thus normalize the "high bone turnover" in elderly osteoporotic patients ("supercoupling"). In addition, it has been shown that D-Hormone analogs are able to increase muscle power and walking distance in elderly D-Hormone deficient patients. Besides the known effect on the vertebral fracture rate, new clinical data confirm that D-Hormone analogs might reduce peripheral fractures by reducing falls. The expanded understanding of the pathogenesis of glucocorticoid- induced osteoporosis with its disturbed calcium homeostasis and the pharmacological effects of alfacalcidol, which counteract such iatrogenic bone loss, contribute to the understanding of its clinical efficacy in this most frequent form of secondary osteoporosis. Due to its recently discovered immunomodulating properties, alfacalcidol might find a slot in the management of bone loss caused by chronic inflammatory diseases or by organ transplantations. Alfacalcidol has multifactorial effects, among which the best known are its anti-bone loss and anti-fracture efficacies in postmenopausal osteoporosis. This demonstrated efficacy is related to its involvement in bone remodelling, leading to an improved bone strength. Its mode of action on muscle power, which reduces falls, is unique, differentiating this form of therapy from all other anti-osteoporotic drugs, none having demonstrated any influence on falls.     

Hemiarthroplasty is an effective surgical method to manage unstable trochanteric fractures in elderly people

Trochanteric femoral fractures are a major problem in the elderly because of higher bone fragility due to osteoporosis. Numerous chronic illnesses, which usually affect the elderly, aggravate and complicate their surgical treatment. Trochanteric femoral fractures results in high morbidity and mortality in elderly patients. The aim of our study is to evaluate the effectiveness of hemiarthroplasty in the treatment of unstable trochanteric femoral fractures in elderly patients. Between 2000 and 2005, 50 patients with unstable trochanteric femoral fractures (41 women) aged 75 to 92 years (mean 86 years) underwent cemented hemiarthroplasty. The surgical procedure was performed within first 48 hours after the fracture (out of which 14 in the first 12 hours, 27 in the first 24 hours and 9 in the first 48 hours), with minimal blood loss. Hemiarthroplasty was indicated in patients where stability was important to allow early mobilization. In forty patients (80%) early ambulation with full weight bearing was achieved during the short period of hospitalization (9-14 days). Given that the affected population is predominantly the elderly, who are less mobile and demanding and thus put less strain on the endoprosthesis, we believe that this kind of treatment is the treatment of choice for unstable trochanteric femoral fractures in these patients. This assumption is corroborated by the fact that we did not have any endoprosthesis luxation, apparent acetabular protrusion or instability during the mean follow up period of 15 months (range 12-18 months).     

Vitamin D and vascular calcification

PURPOSE OF REVIEW: Vascular calcification is frequently found in patients with osteoporosis, atherosclerosis and chronic kidney disease, leading to high morbidity and mortality rates. The effects of vitamin D excess and deficiency on vascular calcification are reviewed in this article. RECENT FINDINGS: There is evidence from experimental studies that mediacalcinosis induced by vitamin D excess is an active and reversible process. Vitamin D excess, however, is rarely seen in the general human population. Experimental data also demonstrate that physiologic vitamin D actions include the inhibition of processes that are important for intimal and medial artery calcification such as pro-inflammatory cytokine release, adhesion molecule release, and proliferation and migration of vascular smooth muscle cells. In uremic rats, low levels of the vitamin D hormone calcitriol are associated with massive vascular and soft tissue calcifications. Whereas retrospective studies already indicate a beneficial effect of active vitamin D on mortality rates in chronic kidney disease, little is yet known about the effect of vitamin D deficiency on cardiovascular morbidity and mortality in the general population. SUMMARY: Available data indicate that vitamin D exerts a biphasic 'dose response' curve on vascular calcification with deleterious consequences not only of vitamin D excess but also of vitamin D deficiency.     

Mechanisms of bone anabolism regulated by statins

Osteoporosis is a common disease in the elderly population. The progress of this disease results in the reduction of bone mass and can increase the incidence of fractures. Drugs presently used clinically can block the aggravation of this disease. However, these drugs cannot increase the bone mass and may result in certain side effects. Statins, also known as HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, have been widely prescribed for CVD (cardiovascular disease) for decades. Nonetheless, several studies have demonstrated that statins exert bone anabolic effect and may be helpful for the treatment of osteoporosis. Several experiments have analysed the mechanisms of bone anabolism regulated by statins. In the present paper, we review the mechanisms of promoting osteogenesis, suppressing osteoblast apoptosis and inhibiting osteoclastogenesis.     

Effects of diet and exercise on plasma vitamin D (25(OH)D) levels in Vietnamese immigrant elderly in Sydney, Australia

Vitamin D deficiency may be associated with osteoporosis and fractures in the elderly. In Australia where there is a sizeable Vietnamese population, research has not yet clarified the roles of diet, exercise and sun exposure in determining vitamin D status. Plasma samples for 25-hydroxy-vitamin D (25(OH)D); dietary intake of vitamin D and calcium; muscle strength and sun exposure were measured and weekly dairy intake, exercise levels and smoking habits were surveyed in free-living elderly of Vietnamese and Australian/British origin. There was marginal vitamin D deficiency (<37 nmol/L 25(OH)D) in 63% of Vietnamese but only in 37% of Australian/British born. Low dairy intake and no vigorous exercise were best predictors of vitamin D deficiency in Vietnamese, taking into account age, gender, dietary intake and sun exposure. Since these migrant elderly may not get adequate sun exposure due to either clothing customs or cultural norms that encourage fair (untanned) skin, it is important to encourage increased exercise and dairy intake.     

Trunk Muscle Activity Is Modified in Osteoporotic Vertebral Fracture and Thoracic Kyphosis with Potential Consequences for Vertebral Health

This study explored inter-relationships between vertebral fracture, thoracic kyphosis and trunk muscle control in elderly people with osteoporosis. Osteoporotic vertebral fractures are associated with increased risk of further vertebral fractures; but underlying mechanisms remain unclear. Several factors may explain this association, including changes in postural alignment (thoracic kyphosis) and altered trunk muscle contraction patterns. Both factors may increase risk of further fracture because of increased vertebral loading and impaired balance, which may increase falls risk. This study compared postural adjustments in 24 individuals with osteoporosis with and without vertebral fracture and with varying degrees of thoracic kyphosis. Trunk muscle electromyographic activity (EMG) associated with voluntary arm movements was recorded and compared between individuals with and without vertebral fracture, and between those with low and high thoracic kyphosis. Overall, elderly participants in the study demonstrated co-contraction of the trunk flexor and extensor muscles during forwards arm movements, but those with vertebral fractures demonstrated a more pronounced co-contraction than those without fracture. Individuals with high thoracic kyphosis demonstrated more pronounced alternating flexor and extensor EMG bursts than those with less kyphosis. Co-contraction of trunk flexor and extensor muscles in older individuals contrasts the alternating bursts of antagonist muscle activity in previous studies of young individuals. This may have several consequences, including altered balance efficacy and the potential for increased compressive loads through the spine. Both of these outcomes may have consequences in a population with fragile vertebrae who are susceptible to fracture.     

Los suplementos de calcio y el posible aumento del riesgo cardiovascular

The primary goal of osteoporosis treatment is to prevent the occurrence of fragility fractures, and thereby reduce morbidity and mortality. Among the various approaches to the treatment of this disease include ensuring proper calcium intake and to obtain adequate levels of vitamin D. Virtually all clinical trials with drugs used to treat osteoporosis systematically include calcium and vitamin D supplements. In light of the recent publication of clinical trials and meta-analyses, a possible increase in cardiovascular risk, particularly in the form of a myocrdial infarction, is hypothesised in patients taking calcium supplements. However, data published to date are inconclusive. Until the development of new scientific evidence, it seems reasonable to recommend, whenever practicable and individualized for each patient, increasing calcium intake with food and reserve supplements for patients with very low calcium intake in the diet. It would also be advisable for the administration of total daily dose to be fractionated throughout the day and with meals, and to obtain appropriate levels of vitamin D (25-hydroxycholecalciferol or calcidiol), along with the basic treatment for osteoporosis that is decided to be prescribed to patients.     

VD缺乏相关疾病及其合理补充的临床意义

：众所周知,人体内维生素D水平与少年佝偻病和老年骨质疏松直接相关。最近大量流行病学证据还表明,维生素D（VD）缺乏是多种自身免疫性疾病,癌症,心血管疾病,抑郁症,老年痴呆症,感染性疾病,肌肉骨骼功能下降等的危险因素之一。另外,胰岛素抵抗,高血压和高胆固醇血症也与维生素D缺乏有关。因此,合理补充维生素D可以降低多种疾病风险,并对心血管疾病的风险有益。本文系根据已有的研究结论,阐述维生素D水平与多种临床疾病之间的关联,并对人体血清VD浓度合理监测及合理补充的临床意义做一综述。     

The effects of calcitriol on falls and fractures and physical performance tests

There is an increase in the incidence of falls with aging and about 10% of falls lead to fractures. Nearly all hip fractures are due to falls and hip fractures are the most severe of the osteoporotic fractures because they lead to a 20% mortality rate and a loss of independent living in 50% of cases. Although there are multiple factors associated with falls, our interest is the role that vitamin D metabolism plays in the pathogenesis of falls. Recent clinical trials show that both vitamin D and the metabolite calcitriol reduce the number of falls by 30-40% in elderly subjects. This should also reduce the number of fractures. In European studies, the decrease in falls could be attributed to an improvement in the muscle weakness that often accompanies vitamin D deficiency. However, in the studies using calcitriol there was no vitamin D deficiency, so the mechanism of its efficacy is less clear. It could be due to increased muscle strength, an improvement in the neurological control of balance or both. Understanding these mechanisms would allow us to search for analogs of vitamin D that act more selectively on muscle and on the central nervous system.     

VD缺乏相关疾病及其合理补充的临床意义

众所周知,人体内维生素D水平与少年佝偻病和老年骨质疏松直接相关。最近大量流行病学证据还表明,维生素D(VD)缺乏是多种自身免疫性疾病,癌症,心血管疾病,抑郁症,老年痴呆症,感染性疾病,肌肉骨骼功能下降等的危险因素之一。另外,胰岛素抵抗,高血压和高胆固醇血症也与维生素D缺乏有关。因此,合理补充维生素D可以降低多种疾病风险,并对心血管疾病的风险有益。本文系根据已有的研究结论,阐述维生素D水平与多种临床疾病之间的关联,并对人体血清VD浓度合理监测及合理补充的临床意义做一综述。     

Vitamin D and disease prevention with special reference to cardiovascular disease

Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25 nmol/l are frequently observed in various population groups throughout the world. This paper highlights the relationship of vitamin D insufficiency with cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases that account for up to 50% of all deaths in western countries. There is evidence from patients with end-stage renal disease that high PTH concentrations are causally related to cardiovascular morbidity and mortality. Activated vitamin D is able to increase survival in this patient group significantly. Moreover, already slightly enhanced PTH concentrations are associated with ventricular hypertrophy and coronary heart disease in the general population. Experimental studies have demonstrated that a lack of vitamin D action leads to hypertension in mice. Some intervention trials have also shown that vitamin D can reduce blood pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is inversely correlated with blood glucose concentrations and insulin resistance. Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the major factor for an insufficient vitamin D status. Unfortunately, vitamin D content of most foods is negligible. Moreover, fortified foods and over-the-counter supplements usually contain inadequate amounts of vitamin D to increase serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to allow higher amounts of vitamin D in fortified foods and supplements.     

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.     

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.     

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.     

Progress in osteoporosis and fracture prevention: focus on postmenopausal women

In the past decade, we have witnessed a revolution in osteoporosis diagnosis and therapeutics. This includes enhanced understanding of basic bone biology, recognizing the severe consequences of fractures in terms of morbidity and short-term re-fracture and mortality risk and case finding based on clinical risks, bone mineral density, new imaging approaches, and contributors to secondary osteoporosis. Medical interventions that reduce fracture risk include sufficient calcium and vitamin D together with a wide spectrum of drug therapies (with antiresorptive, anabolic, or mixed effects). Emerging therapeutic options that target molecules of bone metabolism indicate that the next decade should offer even greater promise for further improving our diagnostic and treatment approaches.     

Hip Fracture,Skeletal Fragility,Osteoporosis and Hormonal Deprivation in Elderly Women

Fractures of the hip have been shown to have a significant personal and societal impact in Western countries; this impact is largely borne by elderly women, and represents a substantial health care commitment in modern society. For many people a fracture of the proximal end of the femur represents a preterminal event of considerable cost, both in economic loss and psychosocial well-being. These fractures are generally recognized as a clinical complication of osteoporosis, and are one index of general skeletal fragility which is also manifested in fractures of the vertebrate and of the distal radius (Colles fracture).There is increasing evidence that hormonal deprivation in elderly women is directly related to loss of skeletal integrity and consequent fragility. There is also increasing evidence that hormonal substitution is effective in preventing this structural loss and fragility. Unfortunately, a therapeutic dilemma has arisen in that the preparation that seems to give optimal protection, conjugated estrogens, has also been reported to cause an increased incidence of endometrial carcinoma. The search for a preparation or dosage regimen of estrogens which simultaneously prevents skeletal atrophy and fragility and avoids the increased risk of malignancy must be a long-term goal.