Aging bone and osteoporosis: strategies for preventing fractures in the elderly

As the older population increases, the incidence of osteoporotic fractures is expected to dramatically rise during the next few decades. Older patients are much more susceptible to fracture at any given bone mineral density (BMD) than are younger patients because of various factors, including the quality of aging bone, which involves more than BMD. Suppression of increased bone turnover by antiresorptive therapies, even with only small changes in BMD, can reduce fracture risk, especially in the lumbar spine. Bisphosphonate treatment can significantly reduce vertebral and nonvertebral fractures, including hip fractures, even in the very elderly. Prospective analyses show that risedronate therapy consistently and significantly reduces the risk of new morphometric vertebral fractures after 1 year in postmenopausal women. Post hoc analyses report significant reductions in the risk of 1 new clinical vertebral fracture after 6 months of risedronate therapy and after 1 year of alendronate therapy. Oral raloxifene therapy and salmon calcitonin nasal spray therapy have been shown to reduce the risk of vertebral fracture after 3 and 5 years, respectively, and post hoc data show a significant reduction in clinical vertebral fracture risk at 1 year with raloxifene use. However, neither raloxifene therapy nor calcitonin therapy reduce the risk of nonvertebral and hip fractures at currently approved doses. Bisphosphonates have been shown to be safe and efficacious with 7 years' risedronate sodium and 10 years' alendronate sodium data published, and bisphosphonates reduce bone turnover and increase BMD to a greater degree than raloxifene and calcitonin, which may partly account for their nonvertebral and hip fracture reduction effect. Therefore, bisphosphonate therapy with risedronate or alendronate should be considered in patients with low BMD at the hip and in older patients with osteoporosis and osteopenia, particularly those with an existing fracture.     

The Treatment of Severe Postmenopausal Osteoporosis

Several chemical entities have shown their ability to reduce axial and/or appendicular fractures in patients with osteoporosis. Since patients who have experienced a previous fracture are at high risk for subsequent vertebral or hip fracture, it is of prime importance to treat such patients with medications that have unequivocally demonstrated their ability to reduce fracture rates in patients with prevalent fractures. Results obtained with calcium and vitamin D, in this particular population, are not fully satisfactory and these medications are probably better used in conjunction with other therapeutic regimens. Bisphosphonates have shown their ability to reduce vertebral (alendronate, risedronate, ibandronate) and non-vertebral (alendronate, risedronate) fractures in patients with established osteoporosis. Raloxifene has also shown similar properties, notwithstanding its effect on non-vertebral fractures, which has only been derived from a post hoc analysis limited to patients with prevalent severe vertebral fractures at baseline. This compound also has interesting non-skeletal benefits, including effects on the breast and heart. Teriparatide, a bone-forming agent, promptly reduces the rate of vertebral and all non-vertebral fractures, without significant adverse effects. Strontium ranelate, the first agent shown to concomitantly decrease bone resorption and stimulate bone formation, has also shown its ability to reduce rates of vertebral and non-vertebral fractures in patients with established osteoporosis. It significantly reduces hip fractures in elderly individuals at high risk for such events. Its safety profile is also excellent.     

Osteoporosis and intake of vitamins

Subclinical vitamins deficiency is common in the elderly, especially in osteoporotic patients. However, most physicians in this area are just focused on drugs for the treatment of osteoporosis. It is already established that several vitamins influence bone turnover, bone mineral density, or even the risk of hip fractures. Improving these vitamins status may help to treat and prevent osteoporosis in elderly people. Recently higher vitamin D intake is recognized to be needed to keep not only bone health but also muscle strength. More sun exposure might be needed for improved bone health in the elderly. Deficiency of Vitamin K, C, or B(12) may be also important modifiable risk factors for osteoporosis and bone fracture. Excessive retinal supplementation may become associated with higher bone loss. Thus such diet rich in fruit and vegetables together with fish and meat could fulfill a balance among these vitamins and should be recommended for prevention or treatment of osteoporosis.     

骨质疏松症及其骨折的局部治疗

骨质疏松症是一种以骨量减少和骨强度降低为表现的骨骼疾病,骨质疏松症患者骨折的风险性显著增加。每年大约有2000万人受到该种疾病的折磨。骨质疏松症是一种无声无息的疾病,往往不被重视和治疗,直到其引起骨折。该病目前主要的治疗手段仍有赖于系统用药以阻止骨密度和骨量的进一步丢失。骨质疏松症的局部治疗是一种新的治疗手段,其通过在易于发生骨质疏松性骨折的部位应用抗骨质疏松药物和促进骨形成的细胞因子或生物材料,达到提高局部骨质疏松骨的骨密度、改善骨微结构和生物力学性质的目的 。     

Osteoporosis in the elderly man

Elderly men are at substantial risk for fracture. Morbidity after osteoporotic fractures appears to be more serious and mortality more common in men than in women. Risk factors for osteoporotic fractures in men appear to be qualitatively similar to those in women. Low bone mineral density (BMD) is an important risk factor for fracture in men; however, further clarification of the relationship between BMD, bone geometry and fracture risk is needed. Our understanding of the mechanisms underlying senile bone loss and the pathogenesis of senile osteoporosis in men remains fragmentary with, in particular, the need for further clarification regarding the precise impact of hormonal status in elderly men on skeletal homeostasis. Nevertheless, the available evidence indicates a role for both testosterone and estrogens in the regulation of bone metabolism in elderly men. Recommendations concerning prevention and treatment of senile osteoporosis in men should focus on the minimization of known risk factors for bone loss and falls. Testosterone treatment may be useful only in those men with initially low serum testosterone. As to other pharmacological treatment modalities, prospective trials specifically in elderly men, and preferably with fracture incidence as the primary clinical endpoint, are required.     

Vertebral fracture assessment using standard bone densitometry equipment predicts incident fractures in women

Vertebral fractures are the most common fracture among the elderly, have a detrimental effect on patients' quality of life, and increase the risk of future fractures. Yet, two-thirds of vertebral fractures remain undiagnosed; therefore, improved detection methods are needed. In this Practice Point commentary, we discuss the study by McCloskey et al., in which low radiation dose imaging with a bone densitometer was used for vertebral fracture assessment (VFA) in a prospective cohort of elderly women. Participants were enrolled in a randomized, double-blind, placebo-controlled trial of the oral bisphosphonate clodronate. Prevalent vertebral fractures detected by VFA were associated with an elevated risk of subsequent osteoporotic fractures, including hip fractures. This finding remained significant after adjustment for age, weight and treatment effect, and in a few instances even after adjustment for femoral BMD. Here, we highlight the importance of identifying vertebral fractures, and the potentially substantial role of VFA in the clinical evaluation and management of patients suspected to have osteoporosis.     

Raloxifene for older women: a review of the literature

Raloxifene is a non-steroidal selective estrogen-receptor modulator (SERM) which is used for prevention and treatment of postmenopausal osteoporosis. Raloxifene decreases the incidence of vertebral fractures by 30%–50% in postmenopausal women with osteoporosis but has not been shown to decrease the incidence of hip fractures or other non-vertebral fractures. At the present time, estrogen-replacement therapy and bisphosphonate treatment are the only medical treatments that are proven to prevent hip fractures with the exception of vitamin D and calcium replacement, which has been shown to prevent hip fractures in elderly individuals and nursing home residents. Raloxifene has been shown to have additive effects on bone turnover and bone mineral density (BMD) when used along with alendronate and teriparatide. Raloxifene could have a role in renal failure as it has been shown to increase BMD of the vertebra over 1 year of therapy. Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer. The increased incidence of venous thromboembolism is the main concern of raloxifene therapy and previous history of venous thromboembolism is a contraindication for use of raloxifene. Raloxifene has a role in treatment of vertebral osteoporosis in older women. The decision to use raloxifene should be based on evaluation of fracture risk and on potential other benefits than fracture reduction along with consideration of side effects.     

Hip fracture in women without osteoporosis

The proportion of fractures that occur in women without osteoporosis has not been fully described, and the characteristics of nonosteoporotic women who fracture are not well understood. We measured total hip bone mineral density (BMD) and baseline characteristics including physical activity, falls, and strength for 8065 women aged 65 yr or older participating in the Study of Osteoporotic Fractures and then followed these women for hip fracture for up to 5 yr after BMD measurement. Among all participants, 17% had osteoporosis (total hip BMD T-score < or = -2.5). Of the 243 women with incident hip fracture, 54% were not osteoporotic at start of follow-up. Nonosteoporotic women who fractured were less likely than osteoporotic women with fracture to have baseline characteristics associated with frailty. Nevertheless, among nonosteoporotic participants, several characteristics increased fracture risk, including advancing age, lack of exercise in the last year, reduced visual contrast sensitivity, falls in the last year, prevalent vertebral fracture, and lower total hip BMD. These findings call attention to the many older women who suffer hip fracture but do not have particularly low antecedent BMD measures and help begin to identify risk factors associated with higher bone density levels.     

Treating osteoporosis to prevent fractures: current concepts and future developments

Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40–70%), nonvertebral (by 25–40%) and hip fractures (by 40–53%) in postmenopausal women with osteoporosis. Due to the risk of rare side‐effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well‐proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk‐based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long‐term fracture prevention and should be the golden standard of future osteoporosis treatment.     

Osteoporosis in men

Osteoporosis is characterized by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Although osteoporosis is generally considered to be a condition affecting post-menopausal women, it is now clear that substantial bone loss occurs with advancing age in men, such that up to 20% of symptomatic vertebral fractures and 30% of hip fractures occur in men. This chapter highlights the incidence and prevalence of osteoporotic fractures in men and reviews the associated morbidity, excess mortality and health and social service expenditure. The determinants of peak bone mass and bone loss in men are discussed, as is the pathogenesis of osteoporosis and vertebral and hip fractures. The criteria for the diagnosis of osteoporosis in men are reviewed, together with the most appropriate investigations for secondary osteoporosis. The management of osteoporosis in men is also discussed, highlighting the most appropriate treatment options.     

Quantitative computed tomography of the lumbar spine,not dual x-ray absorptiometry,is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3).CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.     

Osteoporosis and fractures in postmenopausal women using estrogen

BACKGROUND: Previous studies demonstrate that postmenopausal women who use estrogen are somewhat protected from bone loss and fractures compared with nonusers, but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain. OBJECTIVE: To determine long-term probabilities for incident fractures among postmenopausal estrogen users. METHODS: We examined data from the Study of Osteoporotic Fractures, a prospective cohort study with 10 years of follow-up (1986-1999). This cohort includes 8816 women 65 years and older from community settings in 4 areas of the United States. MAIN OUTCOME MEASURES: Hip, wrist, vertebral, and nonvertebral fractures. RESULTS: At baseline, using criteria developed by the World Health Organization, 40% of continuous estrogen users were osteopenic and 13% were osteoporotic at the hip or spine. Although women currently using estrogen lost less bone density than past users or those who never used estrogen, all user groups on average lost bone from the hip and calcaneus. During 10 years of observation, the adjusted probability of nonvertebral fractures was 19.6% for continuous estrogen users, similar to current partial users and lower than past users and those who never used estrogen (P<.05). These comparisons were similar for hip, wrist, and vertebral fractures. CONCLUSIONS: Although estrogen use is associated with reduced prevalence of low bone density, less bone loss, and lower probabilities for fractures, osteoporosis and fractures are common in older women who used estrogen continuously since menopause. Estrogen users should be considered in strategies designed to detect, prevent, and treat osteoporosis.     

Fracture risk assessment and osteoporosis treatment disparities in 3,970 Japanese patients with rheumatoid arthritis

The aims of this study are to determine the proportion of patients at high risk for major osteoporotic and hip fractures in a Japanese cohort with rheumatoid arthritis (RA) and to determine if a care gap exists for high-risk patients. The Fracture Risk Assessment Tool (FRAX®) was administered to 3,970 Japanese patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis cohort study with (n?=?276) and without (n?=?3,694) the use of bone mineral density (BMD) measurement. The study population had a mean age of 62 years and was 84% female. Among the 1,522 patients ≥65 years of age, 661 (43%) and 1,304 (86%) were at high risk for a major osteoporotic fracture (10-year probability >20%) and hip fracture (>3%), respectively. Among patients at high risk for a major osteoporotic fracture (n?=?723), only 453 (63%) and 320 (44%) reported taking any osteoporosis medications and bisphosphonates, respectively. Among female patients with BMD measurements (n?=?262), the 10-year risk of a major osteoporotic fracture calculated with BMD was significantly higher than in those without BMD measurements (P?相似文献   

How to manage postmenopausal osteoporosis?

Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased fracture risk. Several therapeutic agents are now available to treat postmenopausal osteoporosis and prevent fractures. Combined calcium and vitamin D supplementation reduce the relative risk of non-vertebral fractures by about 18%. Hormone replacement therapy (HRT) should not be prescribed for osteoporosis in women who do not experience menopausal symptoms. The marked benefits of raloxifene on the reduction in invasive breast cancer and vertebral fracture risk are partially counterbalanced by a lack of effect on non-vertebral fracture risk, and an increased risk of venous thromboembolism and stroke. All four bisphosphonates available in Belgium, except ibandronate, have been shown to reduce the risk of vertebral, non-vertebral and hip fractures in prospective, placebo-controlled trials. Globally, the incidence of vertebral fractures is reduced by 41%-70%, and the incidence of non-vertebral fractures by 25%-39%. The anti-fracture efficacy of weekly or monthly doses of oral bisphosphonates has not been directly shown but is assumed from bridging studies based on BMD changes. To date, the various bisphosphonates have not been studied in head-to-head comparative trials with fracture endpoints. There are potential concerns that long-term suppression of bone turnover associated with bisphosphonate treatment may eventually lead to adverse effects, especially atypical femoral fractures and osteonecrosis of the jaw, but these cases are extremely rare. Teri-paratide (recombinant human 1-34 PTH) administered by daily subcutaneous injections decreases by 65% the relative risk of new vertebral fractures in patients with severe osteoporosis. Pivotal trials with strontium ranelate have shown a 41% reduction in new vertebral fractures and a 16% reduction in non-vertebral fractures over 3 years. Denosumab is a fully human monoclonal antibody to RANK Ligand that is administered as a 60-mg subcutaneous injection every 6 months. In the pivotal phase III trial, there was a 68% reduction in the incidence of new vertebral fractures, whereas the incidence of non-vertebral fractures was reduced by 20%. Several new approaches are being explored, including antibodies to sclerostin, cathepsin K inhibitors, src kinase inhibitors, and drugs that act on calcium sensing receptors.     

绝经后妇女脊椎压缩性骨折与骨密度的关系

目的探讨绝经后妇女脊椎压缩性骨折与骨密度（BMD）的关系。方法为病例一对照研究，入选250例有脊椎压缩性骨折的绝经后妇女，另有250名无脊椎压缩性骨折的绝经后妇女作为对照组。两组均有胸腰椎正侧位X线摄片，并应用双能X线吸收仪检测腰椎1～4和左股骨近端各部位BMD。结果脊椎压缩性骨折组身高、体重、腰椎2～4和股骨近端各部位BMD值均显著低于对照组（均P〈0．01）。腰椎2～4BMD是发生脊柱骨折的预报因子（r=-0．416，P〈0．01）。身高和全髋部BMD与骨折次数和骨折椎体数目呈负相关（均P〈0．01）。按股骨颈和全髋部BMD值，骨折组骨质疏松检出率各为50．8％和50．4％；另外剔除在腰椎2～4发生椎体骨折53例，按腰椎2～4BMD检出骨质疏松占64．5％。同时，腰椎2～4、股骨颈或全髋部BMD值低于-2．5s者发生脊柱压缩性骨折的风险分别是BMD正常者的4．76、2．36和3．52倍。结论腰椎呈低骨量是发生脊椎压缩性骨折的重要危险因素。身高的下降和全髋部低BMD值是骨折发生次数和受累椎体数目的危险因子；对绝经后妇女在重视BMD测量的同时，应重视脊柱X线正侧位检查。     

Management of the oldest old with osteoporosis

The incidence of osteoporotic fracture increases with age; the median age for hip fracture, the most serious manifestation of osteoporosis is approximately 83 years. Osteoporotic fracture risk is multifactorial, and is determined by the balance between bone strength and the propensity for falling. Frailty is an independent predictor of falls, hip fractures, hospitalisation, disability and death in the elderly that guides for clinical decision-making, and may emerge as a therapeutic target. Non-pharmacological strategies to reduce fall risk can contribute to prevent osteoporotic fractures. Weight-bearing exercise and balance training programmes are recommended. Nutrition, particularly dietary proteins are of importance in preventing falls and fracture, as well as in fracture rehabilitation. Vitamin D and calcium supplementation is effective in reducing both falls and osteoporotic fractures, including hip fractures. Specific efficacious anti-osteoporosis drugs are underused. The evidence base for the efficacy of most such drugs in the very elderly is incomplete, particularly with regard to nonvertebral and hip fractures. Nonadherence to treatment is a substantial problem, which precludes efficacious therapeutic regimens to fulfil their goals.     

Background for studies on the treatment of male osteoporosis: state of the art

Male osteoporosis represents an important, although long underestimated, public health problem. Both in men and in women aging is accompanied by continuous bone loss and by an exponential increase in the incidence of osteoporotic fracture, with a female to male incidence ratio of about 2 to 3 to 1 in the elderly for hip and vertebral fractures. Morbidity after osteoporotic fractures appears to be more serious and mortality more common in men than in women. To date, no single treatment has been proved to be effective and safe in published prospective studies. The present report, based on a systematic search of the literature on male osteoporosis, summarises the state of the art on the clinical consequences of male osteoporosis and its risk factors, in relation to the present state of knowledge about female osteoporosis. This constitutes the background for the design of rational clinical development strategies for therapeutic interventions in male osteoporosis. From this review of the literature it is apparent that notwithstanding the existing sex differences in pathophysiology of osteoporosis and the difference in age-specific incidence of osteoporotic fractures, there are also important similarities between osteoporosis in women and men. The higher incidence of fracture in women than in men results from quantitative differences in risk factors rather than from different risk factors. Even though there are sex differences in bone geometry, incidence of fracture seems to be similar in men and women for a same absolute areal bone mineral density. However, the lack of data on the changes in fracture rates in men resulting from pharmacological intervention, leading to changes in bone mineral density or bone turnover, remains the main limitation for extrapolation of established treatment outcomes from women to men.     

Osteoporosebehandlung: Bisphosphonate, SERM’s, Teriparatide und Strontium

The therapy of osteoporosis is mostly based upon the use of drugs which inhibit bone resorption. Among these, the bisphosphonate family is the best known and mostly used by clinicians. Both second and third generation bisphosphonates, like alendronate and risedronate, are now available as weekly tablets which have facilitated the patient compliance to treatment together with a decreased occurrence of gastrointestinal side effects. These compounds are used efficiently to treat postmenopausal osteoporosis and osteoporosis of men as well. Their use did provide good evidence of increased bone mineral density (BMD) and a reduction in fracture rates. The use of intravenous bisphosphonates such as Zoledronate, Ibandronate and Pamidronate remains in most of the cases limited to special indications such as intolerance to the oral formulations and treatment of patients with bone metastases. The selective estrogen modulators (SERM's) family is limited to a single product on the market as of now, Raloxifene, which does inhibit bone resorption and is well documented by postmenopausal women to increase BMD and reduce vertebral fractures. In addition, a large range of positive nonosseous effects have been documented such as the reduction of the incidence of breast cancer. Other substances do have a strong anabolic effect such as Teriparatide, a recombinant human formulation of PTH 1-34. This compound has demonstrated good efficacy in postmenopausal women, increasing vertebral and hip BMD and reducing the incidence of fractures at both sites. The exact role of Teriparatide in the clinical setting is still open but its overall impact in the therapy of osteoporosis could be major due to its major efficiency over shorter periods of time. Strontium ranelate, a new divalent Strontium salt taken orally, acts both as an anti-catabolic and anabolic agent. The first results provided with strontium ranelate are very promising due to its major effect on the increase in BMD both at the vertebral and hip sites and its ability to reduce the incidence of fractures at both locations. Additional data are awaited to confirm these initial positive results.     

Pharmacological therapy of osteoporosis

The aim of pharmacological therapy for osteoporosis is to prevent osteoporotic fractures. Low bone mineral density, previous fractures, high values of bone turnover markers, and age are the independent risk factors for osteoporotic vertebral fractures. These clinical parameters should be utilized to start and choose the drugs for osteoporosis.     

Evidence-based review of preventive practice for osteoporosis

Preventive procedures for osteoporosis should aim to eliminate or reduce the risk of osteoporotic fractures later in life. It is important for this purpose to achieve greater peak bone mass during adolescence, to reduce postmenopausal bone loss, and to maintain bone mass and to prevent falls in the elderly. All the available evidences for this topic have been reviewed and evidence-based recommendations for the prevention of osteoporosis and osteoporotic fractures are presented.