Pins and plaster aren't enough: a call for the evaluation and treatment of patients with osteoporotic fractures

A history of an osteoporotic fracture is a powerful predictor of future fractures. Older patients who sustain low trauma fractures are candidates for interventions that should include confirmation of the diagnosis of osteoporosis, adequate calcium and vitamin D administration, and use of an osteoporosis therapy that is proven to lower fracture risk. Recently, however, several reports in the literature have indicated that, in general, those physicians who diagnose and treat fractures, i.e. radiologists, orthopedic surgeons, physiatrists, and those who provide general medical care to these fracture patients, the primary care physicians, are not evaluating patients with acute fractures for the presence of osteoporosis and are not prescribing calcium, vitamin D, or specific pharmacological therapy to reduce future fracture risk. These reports suggest that implementation of a standard of care for the subsequent medical management of the older patient with an acute fracture is needed urgently. Diagnostic tools and several effective therapies exist, but these are underused by the physicians who interface with these patients. A call to action is necessary to reduce the human and economic costs associated with this serious and treatable disease.     

The burden of previous fractures in hip fracture patients. The Break Study

A positive history of fractures in older patients with hip fracture is common. We determined the risk factors associated with a positive history of fractures and the profile of care in hip fracture patients. In the Break Study, we enrolled 1249 women aged ≥60 years, seeking care for a hip fracture. Baseline information included age, body mass index, lifestyle (smoking habit, alcohol consumption), patient's history of fracture after the age of 50 years, family history of fragility fracture and health status (presence of comorbidity, use of specific drugs, pre-fracture walking ability, type of fracture, time to surgery, type of surgery, osteoporosis treatment). In the multivariable model age, smoking, family history, treatment with antiplatelet, anticoagulants and anticonvulsants, were significant predictors of a positive history of fracture. More than 70% of patients underwent surgery more than 48 hours after admission. About 50% were discharged with a treatment for osteoporosis, but more than 30% only with calcium and vitamin D. In conclusion, factors associated with a positive history of fracture are the traditional risk factors, suggesting that they continue to have a negative impact on health even at older ages. Selected drugs, such as antiplatelet and anticoagulants, deserve further consideration as significant factors associated with fractures. Given that delay in surgery is a major cause of mortality and disability, while treatment for osteoporosis decreases significantly the risk of recurrent fractures and disability, interventions to modify these patterns of care are urgently needed.     

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.     

Diagnosis and management of vertebral fractures in elderly adults

We reviewed the epidemiology, diagnosis, and treatment of vertebral fractures due to osteoporosis in the elderly. Vertebral fractures are underdiagnosed despite their high prevalence in both men and women. Clinical consequences of vertebral fractures include increased risk of future vertebral and hip fracture, acute and chronic back pain, decreased quality of life, and increased mortality. Patients with vertebral fractures have functional impairment and increased mortality similar to those with hip fractures. Asymptomatic fractures identified on radiograph also affect quality of life and mortality. A vertebral fracture is a clinical marker for a subsequent fracture and should trigger assessment and diagnosis of osteoporosis. The care of patients with vertebral fractures includes pain management, rehabilitation, and prevention of further fractures. There is evidence from randomized controlled trials that pharmacologic therapy can reduce the risk of future fractures by 40% to 50%. Vertebroplasty may be effective in the control of pain and in obtaining stability of the spine.     

Selection of individuals for prevention of fractures due to bone fragility.

Most patients with fractures go untreated because of the lack of awareness of osteoporosis. Treatment is indicated for women and men with osteoporosis and women and men with fractures with either osteoporosis or osteopenia because (a) fractures increase morbidity and mortality, (b) the burden of fractures is increasing because longevity is increasing, and (c) bone loss accelerates, rather than decelerates in old age. The indication for drug therapy is less clear in women or men with osteopenia because drugs have not been proved to reduce fracture risk in this group. There is no evidence that treating individuals with only risk factors reduces the fracture rate. Screening has not been shown to reduce the burden of fractures. Altering the bone mineral density by a few percent in the population is likely to reduce the number of fractures, but how this can be achieved is unknown. The rigorously investigated drugs reducing the spine fracture rate are alendronate, raloxifene and risedronate. Calcium and vitamin D reduce hip fractures in nursing home residents but not community-dwellers. In the community, only alendronate and risedronate have been reported to reduce hip fractures in randomized trials. The evidence for hormone replacement therapy is less satisfactory. It is likely to reduce the number of spinal fractures, but its role in hip fracture prevention is uncertain. Only alendronate has been reported to reduce spine fractures in men with osteoporosis. Evidence for the use of other drugs (calcitonin, fluoride, anabolic steroids and active vitamin D metabolites) in women or men is insufficient to justify their use.     

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.     

Advances in osteoporosis: better identification of risk factors can reduce morbidity and mortality

Johnell O (Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden). Advances in osteoporosis: better identification of risk factors can reduce morbidity and mortality (Review). J Intern Med 1996; 239: 299–304.
Osteoporosis is a common disease of postmenopausal women and the elderly. Low bone mass results from genetic, nutritional and lifestyle factors, decreased oestrogen levels, certain medical conditions, and the use of certain drugs. The overall incidence and age-and sex-related incidences of osteoporosis are increasing worldwide. Osteoporotic fractures can cause considerable pain, disability, loss of independence and deterioration in quality of life. Many patients lose the ability to perform the activities of daily living. Mortality and morbidity after hip fracture increase with age. Prevention of osteoporosis and osteoporotic fractures is an urgent priority to reduce the burden placed on health care and social welfare systems.     

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.     

Bisphosphonate therapy for secondary osteoporosis: adult perspective

BACKGROUND: A number of disease states and drugs can upset the balance between bone formation and resorption resulting in increased fracture risk. Glucocorticoids are the most recognized cause of secondary osteoporosis. Hypogonadism, weight loss, and chronic inflammation are other contributors to bone loss in a variety of disease states. Bisphosphonates are potent inhibitors of bone resorption, and there is a variety of secondary osteoporosis where they produce substantial increases in bone density and reduce fracture risk by about 50%. Upper gastrointestinal tract intolerance with oral agents and a flu-like syndrome with intravenous bisphosphonates are the principal adverse effects associated with their use. CONCLUSIONS: Numerous disease states and medications can adversely affect the skeleton. Additional effects of aging and menopause can substantially increase an individual's fracture risk. It is important that physicians assess fracture risk in susceptible patients and initiate treatment when indicated.     

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.     

Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures

Glucocorticoids are the most common cause of drug-related osteoporosis. We reviewed current evidence on risk factors for glucocorticoid-induced osteoporosis (GIOP) and prevention and treatment of GIOP-related fractures. Guidelines for GIOP management published since 2000 were also reviewed. Significant bone loss and increased fracture risk is seen with daily prednisone doses as low as 5 mg. Alternate-day glucocorticoid therapy can lead to similar bone loss. No conclusive evidence exists for a safe minimum dose or duration of glucocorticoid exposure. Physicians should consider risk factors for involutional osteoporosis such as older age, postmenopausal status, and baseline bone density measurements as they assess patients for prevention or treatment of GIOP. Bisphosphonates were reported to reduce GIOP-related vertebral fractures, but inconclusive data exist for hip fractures associated with glucocorticoid use. Hormone replacement therapy and parathyroid hormone analogs are effective in preserving bone density in GIOP. The risk of osteoporosis and fractures should be routinely assessed in patients receiving glucocorticoid therapy. Effective prevention and treatment options are available and can result in meaningful reduction of GIOP-related morbidity and mortality. Current guidelines for GIOP management recommend bisphosphonates, especially alendronate and risedronate, as first-line agents for GIOP, and these guidelines propose the preventive use of bisphosphonates early in the course of glucocorticoid therapy in high-risk patient subgroups.     

Male osteoporosis-what are the causes,diagnostic challenges,and management

Osteoporosis is underrecognized and undertreated in men, even though up to 25% of fractures in patients over the age of 50 years occur in men. Men develop osteoporosis with normal aging and accumulation of comorbidities that cause bone loss. Secondary causes of bone loss may be found in up to 60% of men with osteoporosis. Mortality in men who experience major fragility fracture is greater than in women. Diagnosis of osteoporosis in men is similar to women, based on low-trauma or fragility fractures, and/or bone mineral density dual-energy X-ray absorptiometry (DXA) T-scores at or below ?2.5. Because most clinical trials with osteoporosis drugs in men were based on bone density endpoints, not fracture reduction, the antifracture efficacy of approved treatments in men is not as well documented as that in women. Men at a high risk of fracture should be offered treatment to reduce future fractures.     

Osteoporosis: strategies for prevention and management

Osteoporosis is a serious public health issue, affecting up to 1 in 2 women and 1 in 5 men over the age of 50 years. The common osteoporotic fractures occur at the spine, wrist and hip. For the patient affected by osteoporosis, these fractures are associated with significant morbidity and, in the case of hip and spine fractures, an excess mortality. The treatment of osteoporotic fractures is also associated with a significant healthcare cost for society. Currently, measurement of bone mineral density using dual energy X-ray absorptiometry is the gold standard for the diagnosis of osteoporosis. In the future, however, assessment of fracture risk will be based on algorithms incorporating clinical risk factors and bone density measurements, where appropriate. The goal of treatment is to reduce the risk of future fracture. Patients at high risk for fracture should be assessed and screened to exclude secondary causes for osteoporosis. Bisphosphonates (alendronate, etidronate, ibandronate, risedronate) are the first-line therapy for the majority of patients and these treatments can be given either orally or intravenously. Alternative treatment options include strontium ranelate and raloxifene. Anabolic therapy with parathyroid hormone can be considered for patients with severe disease. These patients will often require referral for specialist assessment and monitoring. All patients at risk of developing osteoporosis should be given lifestyle advice regarding dietary intake of calcium and vitamin D and regular weight-bearing exercise.     

Steroid induced osteoporosis: prevention and treatment

PURPOSE: Corticosteroid induced osteoporosis (CIO) is the most frequent complication of long-term corticosteroid therapy, and the most frequent cause of secondary osteoporosis. New data from biological, epidemiological and therapeutic studies provide basis for optimal management of this bone disease. MAIN POINTS: Corticosteroids are responsible for both quantitative and qualitative deleterious effects on bone, through their effect on bone cells, mainly on osteoblasts (with both a decrease in osteoblast activity and an increase in apoptosis). Epidemiological studies have shown an increased risk of fractures related to CIO, even for low doses, and during the first 6 months of treatment. Relative risk is 1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral density, measured by dual-energy X-ray absorptiometry, is decreased at spine and hip; the risk of fracture is higher in CIO as compared to post-menopausal osteoporosis, for a similar bone density. Prevention of CIO needs the use of the minimal efficacious dose, and treatment of calcium, vitamin D and gonadal hormones insufficiencies. Patients at risk of fracture, as post-menopausal women with prevalent fractures, should receive a bisphosphonate. PERSPECTIVE: It may be possible to reduce the fracture risk in patients on long-term corticosteroid therapy.     

Efficacy,effectiveness and side effects of medications used to prevent fractures

There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long‐term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit–risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and ‘drug holidays’ should be considered at this time. Further studies are needed to guide clinical practice in this area.     

Osteoporosis in men: Are we ready to diagnose and treat?

Because osteoporosis and its attendant fractures are more common in women than in men, most studies have been performed in women. However, age-related osteoporosis and fragility fractures are also a major problem in men. Recent studies suggest that diagnosing men as osteoporotic when they fall more than 2.5 standard deviations below the mean for young men identifies a group at risk for fracture. Data suggest that many men with femoral fractures have age-related hypogonadism. Hypogonadism is associated with decreased lean body mass and bone mass. Most men with femoral fractures are reported to be hypogonadal. Testosterone replacement in hypogonadal older men improves bone mass and lean body mass. A therapeutic intervention to reduce fracture incidence in men with osteoporosis has been reported. No population-based study has examined the incidence or prevalence of hypogonadism with or without osteoporosis in men. Thus, osteoporosis in men probably exists with and without hypogonadism. Therapeutic interventions should be based on treatment of hypogonadism when present with osteoporosis.     

Redefining osteoporosis treatment: Who to treat and how long to treat

Osteoporosis is a common disease that is associated with increased risk of fractures and serious clinical consequences. Bone mineral density (BMD) testing is used to diagnose osteoporosis, estimate the risk of fracture, and monitor changes in BMD over time. Combining clinical risk factors for fracture with BMD is a better predictor of fracture risk than BMD or clinical risk factors alone. Methodologies are being developed to use BMD and validated risk factors to estimate the 10-year probability of fracture, and then combine fracture probability with country-specific economic assumptions to determine cost-effective intervention thresholds. The decision to treat is based on factors that also include availability of therapy, patient preferences, and co-morbidities. All patients benefit from nonpharmacological lifestyle treatments such a weight-bearing exercise, adequate intake of calcium and vitamin D, fall prevention, avoidance of cigarette smoking and bone-toxic drugs, and moderation of alcohol intake. Patients at high risk for fracture should be considered for pharmacological therapy, which can reduce fracture risk by about 50%.     

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.     

Emerging anabolic treatments for osteoporosis

Therapy for osteoporosis is principally centered on the use of agents that block bone resorption and supplementation with vitamin D and calcium. Although these drugs are effective in reducing the risk of subsequent fractures, and modestly increasing bone density, most patients being treated for osteoporosis still have low bone mass and a greater risk of fracture. Anabolic agents stimulate bone formation, strength, and mass. In addition, there is emerging evidence that anabolic agents can reduce subsequent fracture risk. The two most promising agents, parathyroid hormone (PTH) and GH/IGF-I, act to increase osteoblast mediated bone formation. A review of the potential usefulness of PTH and GH/IGF-I is presented.     

Hip fracture protection by alendronate treatment in postmenopausal women with osteoporosis: a review of the literature

Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. In particular, hip fractures are an important cause of mortality and morbidity among postmenopausal women. Anti-resorptive therapies that produce greater decreases in bone turnover markers together with greater increases in bone mineral density (BMD) are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Thus, treatment with potent anti-resorptive drugs like alendronate is a strategy for preventing hip fractures in postmenopausal women with osteoporosis. The purpose of this paper is to discuss the efficacy of alendronate against hip fractures and the mechanism for this anti-fracture efficacy in postmenopausal women with osteoporosis. A meta-analysis of randomized controlled trials has shown that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis. According to the analyses of the Fracture Intervention Trial, each 1 standard deviation reduction in a 1-year change in bone-specific alkaline phosphatase (BSAP) is associated with 39% fewer hip fractures in alendronate-treated postmenopausal women, and those with at least 30% reduction in BSAP have a 74% lower risk of hip fractures relative to those with less than 30%. Alendronate is effective in reducing the risk of hip fractures across a spectrum of ages. The mechanism for this anti-fracture efficacy has been clarified; alendronate strongly suppresses bone turnover and subsequently increases hip BMD, decreases cortical porosity, improves parameters of hip structure geometry (cortical thickness, cross-sectional area, section modulus, and buckling ratio), and produces more uniform mineralization (increases the mean degree of mineralization of bone) in cortical bone. A once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment than the once-daily dosing regimen, leading to greater efficacy against hip fractures. Thus, the efficacy of alendronate against hip fractures has been confirmed in postmenopausal women with osteoporosis, especially with a once-weekly dosing regimen.