Pharmacological treatment of osteoporosis for people over 70

Osteoporosis has been defined as "a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture". The impact of osteoporosis is most pronounced in elderly populations who run the greatest risk of fractures. The probability of developing mainly hip, vertebral and other non-vertebral fractures (for example, a Colles fracture) not only depends on bone mineral density (BMD) but also on age. Older patients are more susceptible to fracture than younger patients with the same BMD T-score. As the older population increases, the incidence of osteoporotic fractures is expected to rise dramatically over the next few decades. Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss and kyphosis. These changes may result in significant declines in physical performance, function and, ultimately, loss of independence. The challenge for physicians is to prevent bone loss, to diagnose and treat osteoporosis before fractures occur, and to treat patients who have already experienced a fracture to prevent recurrent fractures. The objective of this review is to analyze the capacity to reduce fractures as the key element to evaluate the effectiveness of available medications: calcium and Vitamin D, bone formation drugs, antiresortive drugs, and dual-effect drugs. In view of the paucity of information about treatment of osteoporosis in the elderly population, available studies were not designed with this objective, so that this article reviews data mostly deriving from post-hoc analysis or sub-analysis of the main phase III clinical trials of each of the tested medications.     

Physical activity, falls, and fractures among older adults: a review of the epidemiologic evidence

OBJECTIVES: Assess the relationship between physical activity and risk for falls and osteoporotic fractures among older adults. DESIGN: Review and synthesis of published literature. MEASUREMENTS: We searched the literature using MEDLINE, Current Contents, and the bibliographies of articles identified. We included randomized controlled trials (RCT) of the effects of physical activity on the incidence of falls and case-control and prospective cohort studies of the association of physical activity with osteoporotic fracture risk. We also summarized mechanisms whereby physical activity may influence risk for falls and fractures. RESULTS: Observational epidemiologic studies and randomized clinical trials evaluating the effectiveness of physical activity programs to prevent falls have been inconclusive. However, many studies have lacked adequate statistical power, and recent trials suggest that exercise, particularly involving balance and lower extremity strength training, may reduce risk of falling. There is consistent evidence from prospective and case-control studies that physical activity is associated with a 20-40% reduced risk of hip fracture relative to sedentary individuals. The few studies that have examined the association between physical activity and risk of other common osteoporotic fractures, such as vertebral and wrist fractures, have not found physical activity to be protective. CONCLUSIONS: Epidemiologic studies suggest that higher levels of leisure time physical activity prevent hip fractures and RCTs suggest certain exercise programs may reduce risk of falls. Future research needs to evaluate the types and quantity of physical activity needed for optimal protection from falls and identify which populations will benefit most from exercise.     

Genetic liability to fractures in the elderly

BACKGROUND: The genetic impact on the causation of osteoporotic fractures is unclear. A large twin study is ideally suited to determine the genetic liability to categories of fracture at various ages. METHODS: A cohort of all 33 432 Swedish twins born from 1896 to 1944 was used to evaluate the genetic liability to fracture occurrence in the elderly. The Swedish Inpatient Registry and computer-assisted telephone interviews enabled us to identify 6021 twins with any fracture, 3599 with an osteoporotic fracture, and 1055 with a hip fracture after the age of 50 years. RESULTS: Genetic variation in liability to fracture differed considerably by type of fracture and age. Less than 20% of the overall age-adjusted fracture variance was explained by genetic variation. The age-adjusted heritability of any osteoporotic fracture was slightly greater (0.27; 95% confidence interval [CI], 0.09-0.28), and for hip fracture alone, it was 0.48 (95% CI, 0.28-0.57). Heritability was not attenuated after further adjustment for several known osteoporotic covariates but was considerably greater for first hip fractures before the age of 69 years (0.68; 95% CI, 0.41-0.78) and between 69 and 79 years (0.47; 95% CI, 0.04-0.62) than for hip fractures after 79 years of age (0.03; 95% CI, 0.00-0.26). CONCLUSIONS: The importance of genetic factors in propensity to fractures depends on fracture site and age. The search for susceptibility genes and environmental factors that may modulate expression of these genes in younger elderly patients with hip fracture, the most devastating osteoporotic fracture, should be encouraged. Prevention of fractures in the oldest elderly should focus on lifestyle interventions.     

Are patients with hip fractures more osteoporotic? Review of the evidence

This report critically reviews 15 case-control studies that disagree about whether patients who fracture their hip are significantly more osteoporotic than persons of similar age who do not. The most rigorously designed studies observed less bone mass in the hips of patients with fractures than in the hips of control subjects, but the differences were usually small and overlapping. Measurements at other sites in the skeleton did not consistently find differences. Those studies that protected against ascertainment bias generally found smaller differences than studies that did not. Patients with hip fractures do not appear to be distinctly more osteoporotic than persons of similar age. Therefore, factors besides bone mass, such as a tendency to fall, may be important determinants of which elderly persons will have fractures; thus, measurements of bone mass might not be a reliable way to identify those at greatest risk of hip fracture.     

Leitliniengerechte Diagnostik und Therapie der Osteoporose 2010

Osteoporotic fractures are a frequent cause of disability and loss of quality of life in old age. Maintaining muscle function and balance, a daily calcium intake of 1000 mg, sufficient vitamin D and prudent use of drugs associated with falls and osteoporosis are key components to fracture prevention. The German guideline recommends that a specific long-term osteoporosis medication be initiated in individuals with a 30% 10-year risk for hip fractures and vertebral fractures.     

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.     

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.     

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.     

Osteoporosis and osteoporotic fractures in men: a clinical perspective.

The lifetime risk of any fracture of the hip, spine or distal forearm in men aged 50 years has been estimated to be 13%, compared with 40% in women. Although the overall incidence of osteoporosis is less in men than in women, the disease still represents an important public health problem. In particular, hip fractures are associated with substantial mortality and morbidity, even more so than in women. In male patients presenting with osteoporotic fractures, major causes of skeletal fragility, such as hypogonadism, glucocorticoid excess, primary hyperparathyroidism and alcohol abuse, can often be identified. In as many as 50% of osteoporotic men, however, no aetiology can be found: these men suffer from a syndrome commonly referred to as idiopathic osteoporosis, which is presumably related to some type of osteoblast dysfunction. Recent evidence indicates that the loss of skeletal integrity in ageing men may be partially related to endocrine deficiencies, including vitamin D, androgen and/or oestrogen deficiency. While the consequences of vitamin D or oestrogen deficiency in women have been well established, the skeletal impact of these (partial) age-related deficiencies in men remains to be clarified. Osteoporosis in elderly men is a multifactorial disease, as it is in women. The prevention of osteoporosis should therefore focus not only on increasing the bone strength, but also on decreasing the risk of falls. However, the prevention and therapy of osteoporotic disorders in men are virtually unexplored. To date, the use of specific osteoporotic drugs in osteoporotic men is still based on reasonable but untested assumptions.     

Prevention of osteoporotic fractures in the elderly

Osteoporosis is a common and preventable disorder of the older adult skeleton that predisposes an individual to an increased risk of fracture, a major cause of disability in older adults. Most patients with osteoporosis have an identifiable cause of bone loss. Factors contributing to osteoporotic fractures are more often associated with disordered neuromuscular function affecting postural stability than disordered skeletal integrity. Effective pharmacologic agents are available for the prevention and treatment of osteoporosis. Prevention of osteoporotic fractures in the elderly, particularly nonvertebral fractures, presents unique challenges. Fracture prevention requires identification and management of disorders that contribute to falls, the prevention of falls, and reduction of the impact force of falls. Thus, both pharmacological and nonpharmacological strategies need to be employed. The presence of multiple co-morbidities further complicates management of osteoporosis in the elderly population.     

Intervention in lifestyle factors for the prevention of osteoporosis and osteoporotic fractures

According that osteoporosis is the common condition in an aging society such as in Japan, much progress has been made in understanding the treatment and prevention of osteoporosis. Among potential risk factors, exercise, smoking, and alcohol consumption have been recognised as important lifestyle factors that might influence the risk of osteoporosis and osteoporotic fractures. To assess the relationship between these lifestyle factors and the risk for low bone mass and osteoporosis-related fractures, a systematic literature search over past 13 years was conducted. Accumulating evidence indicates that exercises decrease the risk for hip fractures among middle aged and older men and women. Exercises also help to maintain muscle strength, muscle volume, balance, and joint flexibility, which might prevent falls and fall-related fractures. One randomised controlled trial indicates that high-impact and/or weight-bearing exercise might increase the bone density in the elderly and the peak bone mass among young women. The literature search also address that there is an association between cigarette smoking and the risk of osteoporosis. Smoking cessation is effective to decrease the risk for both osteoporosis and osteoporotic fractures. Future research should be required to evaluate the alcohol consumption and osteoporosis.     

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.     

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.     

Does the combination of a simultaneous subcapital fracture of humerus and hip fracture in elderly patients carry a prognostic value?

The most important factor to cause hip fractures in elderly is probably osteoporosis. Other factors are the increase in fall frequency and the protective response to trauma. Osteoporotic fractures occur most commonly, at the hip, vertebra, distal radius and proximal humerus. A combination of these is uncommon. Thirty-two women and six men treated between January 1990 and December 1999 for a combination of subcapital fracture of the humerus and hip fractures were evaluated retrospectively. The following parameters were reviewed: age, sex, pre-fall function, use of drugs, chronic and acute comorbidity, circumstances of the fall, length of hospitalization, treatment procedure, complications and post-hospitalization rehabilitation. Group I consisted of 15 patients aged 70-80 years and group II consisted of the remaining 23 patients, older than 80 years. In all 38 patients the simultaneous fractures were ipsilaterally. Hospital stay ranged from 7 to 17 days for the discharged 37 patients. Twenty-six of 28 patients, who were transferred to a rehabilitation center, returned to their previous activity of daily living (ADL). Among the nine remaining patients only five gained full recovery. A combination of fractures, occurs in the higher-age group, is quite traumatic to the patient and probably involves a greater impact force. In all patients it occurs in the ipsilateral side. In the elderly, even a minimal transmission to the osteoporotic hip can cause a fracture. The double trauma represents a better pre-morbid condition relative to patients in the same age group, thus it may serve as a prognostic indicator for success in rehabilitation.     

Treatment of postmenopausal osteoporosis

The aim of treatment of postmenopausal osteoporosis is to reduce the frequency of vertebral and non-vertebral fractures (especially at the hip), which are responsible for morbidity associated with the disease. Results of large placebo controlled trials have shown that alendronate, raloxifene, risedronate, the 1-34 fragment of parathyroid hormone, and nasal calcitonin, greatly reduce the risk of vertebral fractures. Furthermore, a large reduction of non-vertebral fractures has been shown for alendronate, risedronate, and the 1-34 fragment of parathyroid hormone. Calcium and vitamin D supplementation is not sufficient to treat individuals with osteoporosis but is useful, especially in elderly women in care homes. Hormone replacement therapy remains a valuable option for the prevention of osteoporosis in early postmenopausal women. Choice of treatment depends on age, the presence or absence of prevalent fractures, especially at the spine, and the degree of bone mineral density measured at the spine and hip. Non-pharmacological interventions include adequate calcium intake and diet, selected exercise programmes, reduction of other risk factors for osteoporotic fractures, and reduction of the risk of falls in elderly individuals.     

Osteoporosis considerations in the frail elderly

Osteoporosis is a growing public health problem throughout the world, in part because of the increasing numbers of people living beyond the age of 65 years. Skeletal fractures are the clinical manifestation of the disease, with older patients the most severely affected. Conditions associated with frailty such as falls and reduced muscle strength likely contribute to fractures, causing substantial mortality, morbidity, and economic cost. Screening guidelines for osteoporosis have been issued recently and take into account multiple risk factors for this condition. Falls are the chief mechanism by which osteoporotic fractures occur. Nonpharmacologic interventions for osteoporosis mainly address fall and frailty prevention, whereas pharmacologic interventions target bone loss through decreasing bone resorption, increasing bone formation, or a combination of both processes. Although guidelines for intervention strategies are in flux, it is now suggested that absolute fracture risk rather than diagnostic thresholds be used to determine the timing for therapeutic intervention. Individual risks and benefits of therapies need to be considered before choosing a therapeutic regimen.     

Adverse skeletal effects of drugs – beyond Glucocorticoids

Osteoporotic fractures are an important public health problem with significant individual and societal costs. In addition to the major risk factors for osteoporotic fracture, low bone mineral density (BMD), age, low body weight and history of fracture or falls, some drugs are now considered to be important secondary risk factor for bone loss and fracture, particularly amongst predisposed individuals. Currently available data are often generated from small observational clinical studies, making risk assessment and development of management guidelines difficult. In many cases, the exposed population has a low baseline risk for fracture and additional assessment and treatment may not be necessary. In this review, we focus on drugs other than glucocorticoids identified as potentially causing adverse skeletal effects, summarizing the existing evidence from preclinical and clinical studies, and suggest recommendations for patient management.     

Postmenopausal osteoporosis: fracture consequences and treatment efficacy vary by skeletal site

At least half of all postmenopausal women will experience fractures during their lifetime, and the consequences are often serious, but most women at risk are not receiving adequate treatment. The objective of this paper is to summarize the literature concerning the consequences of osteoporotic fractures, and the effectiveness of pharmacologic agents for preventing fractures and their consequences, emphasizing a systematic, evidence-based summary of treatment results from randomized, controlled trials that were published previously. Osteoporosis is associated with increased risk of fractures at most skeletal sites. Hip fractures have much greater prognostic significance in terms of health than any other single type of fracture. However, symptomatic vertebral fractures and other non-hip fractures also represent enormous morbidity and economic burdens, and signal increased risk of future fractures of all types, including the hip. There is convincing evidence that two bisphosphonates (alendronate and risedronate) reduce the risk of both spine and non-spine fractures. The evidence for reducing hip fracture risk is greater for alendronate, with a consistent approximately 50% reduction in hip fractures across studies. Alendronate has also been demonstrated to maintain quality of life by reducing outcomes such as hospitalization and bed rest related to back pain. Among other agents, raloxifene reduces the risk of vertebral fractures by approximately 30%; the published evidence for most other agents is inconclusive. Osteoporosis should be regarded as seriously as other important chronic disorders such as hypertension and hyperlipidemia. Postmenopausal patients with a high risk of fractures--such as those with prior fractures or osteoporosis as measured by BMD--need to be treated. Although other therapeutic modalities are available, the evidence is most convincing for the bisphosphonates, alendronate and risedronate.     

Serum fructosamine level and the risk of hip fracture in elderly women: a case-cohort study within the study of osteoporotic fractures

PURPOSE: While a high serum fructosamine level may be an indicator of undiagnosed diabetes, a low level may be indicative of poor nutrition or frailty. As malnutrition is a risk factor for osteoporosis, low serum fructosamine levels may be associated with an increased risk of osteoporotic fracture. We examined the association between serum fructosamine levels and the risk of subsequent hip and vertebral fracture.SUBJECTS AND METHODS: We performed a case-cohort study within the Study of Osteoporotic Fractures. Subjects were elderly, ambulatory, community-dwelling, Caucasian, women. Fructosamine levels were measured in baseline serum. Incident vertebral fractures were identified by comparing baseline spinal radiographs to those obtained an average of 3.5 years later. Hip fractures were confirmed by radiograph. We randomly selected 101 women who suffered a hip fracture, 100 women who developed a vertebral fracture, and 276 controls. We compared fructosamine levels in women with subsequent osteoporotic fractures to controls. All analyses were adjusted for age, weight, and use of estrogens.RESULTS: Women with fructosamine levels in the lowest decile (≤223 μmol/L) had a three-fold increase in the risk of hip fracture (95% confidence interval 1.4–6.4), compared with all other women. Adjustment for markers of frailty, including smoking, functional status, and serum albumin levels, reduced the strength of this association. No clear association was observed between serum fructosamine level and the risk of vertebral fracture.CONCLUSION: Low serum fructosamine levels, which likely reflect frailty or malnutrition, may be a useful clinical tool to identify women at risk for hip fracture.