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.     

Is there a place for bone turnover markers in the assessment of osteoporosis and its treatment?

As populations age, the number of osteoporotic fractures will increase. Bone mineral density (BMD) measurement remains the major way to diagnose osteoporosis and to indicate therapy. The FRAX tool, based on clinical risk factors, estimates the 10-year risk of hip and major osteoporotic fractures. The association of BMD and FRAX measurements has improved the identification of patients who are most at risk. However, some patients can still be overlooked and denied therapy. It is sound that adding the measure of bone turnover markers to the former risk factors and their follow-up during therapy could best address the efficacy of treatment of osteoporosis. Whether this behavior is cost-effective remains to be settled.     

Evaluation and treatment of bone disease after fragility fracture

Bone mineral density and other measuring tests are part of the risk assessment of primary and secondary osteoporosis necessary in treating patients after fragility fracture. A better understanding of factors contributing to insufficiency fracture in osteoporotic bone is essential to guide the clinician's intervention in this disease affecting 25 million women in the United States and responsible for an estimated 700,000 vertebral and 300,000 hip fractures every year. Prevention of future fractures by slowing or stopping bone loss, maintaining bone strength, and minimizing or eliminating factors contributing to fractures, through pharmacotherapy, education, and lifestyle changes, can help slow annual health care expenditures for osteoporotic fractures, which now exceed 17 billion dollars, more than for breast and gynecological cancers combined.     

Bone mineral density thresholds for pharmacological intervention to prevent fractures

BACKGROUND: Treatment intervention thresholds for prevention of osteoporotic fractures can be derived from reports from the World Health Organization (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria). It is not known how well these thresholds work to identify women who will fracture and are therefore candidates for treatment interventions. We used data from the National Osteoporosis Risk Assessment (NORA) to examine the effect of different treatment thresholds on fracture incidence and numbers of women with fractures within the year following bone mineral density measurement. METHODS: The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean age, 64.5 years). At baseline, bone mineral density was assessed by peripheral bone densitometry at the heel, finger, or forearm. New fractures during the next 12 months were self-reported. RESULTS: New fractures were reported by 2259 women, including 393 hip fractures; only 6.4% had baseline T scores of -2.5 or less (World Health Organization definition for osteoporosis). Although fracture rates were highest in these women, they experienced only 18% of the osteoporotic fractures and 26% of the hip fractures. By National Osteoporosis Foundation treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or -1.5 or less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of osteoporotic fractures and 53% of hip fractures occurred in these women. CONCLUSIONS: Using peripheral measurement devices, 82% of postmenopausal women with fractures had T scores better than -2.5. A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.     

Basics and management of glucocorticoid-induced osteoporosis

Glucocorticoids interfere with bone metabolism at different levels. Therefore, glucocorticoid-induced osteoporosis (GIO) is the most frequent form of secondary osteoporosis and up to 50 percent of patients on chronic glucocorticoid therapy suffer fractures. This is also because GIO is still under-diagnosed and not adequately treated. Besides, the fracture risk is higher in GIO than in primary osteoporosis even in the presence of equal bone mass density. The risk of osteoporotic fractures increases with dose and duration of glucocorticoid therapy, although the loss of bone mass is more prominent within the first three to twelve months after initiation of treatment. Besides glucocorticoid treatment, other factors, such as e.g. the underlying disease, substantially influence the fracture risk. Therefore, a diagnostic screening is mandatory in each case and should include the patient's history, physical examination, laboratory studies, evaluation of the bone-mass density by dual X-ray absorptiometry and imaging of the spine. Education of the patients and pharmacological prevention are very important, antiresorptive therapy has to be started earlier than in primary osteoporosis and osteoanabolic agents have also been proven to be effective.     

Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis

Bisphosphonates have been shown to increase bone mineral density in patients with established osteoporosis as well as those with osteopenia. The evidence conclusively shows a reduction in fracture rates in patients on the more potent nitrogen containing bisphosphonates. Indeed, significant vertebral fracture rate reduction has been demonstrated after only 1 year of therapy. Alendronate, a second-generation bisphosphonate, and risedronate, a third-generation bisphosphonate, are first line medications for the treatment of osteoporosis given their efficacy in preventing both vertebral and non-vertebral fractures. There is evidence that vertebral fractures may be prevented by intermittent cyclic therapy with etidronate. All three have been shown to increase bone mineral density in the spine, with alendronate and risedronate producing significant increases in hip bone density. Calcitonin has demonstrated the ability to reduce vertebral fracture rates with minimal changes in bone density. Calcitonin is also beneficial in reducing the bone pain associated with fractures.     

Grundlagen und Management der glukokortikoidinduzierten Osteoporose

Glucocorticoids interfere with bone metabolism at different levels. Therefore, glucocorticoid-induced osteoporosis (GIO) is the most frequent form of secondary osteoporosis and up to 50 percent of patients on chronic glucocorticoid therapy suffer fractures. This is also because GIO is still under-diagnosed and not adequately treated. Besides, the fracture risk is higher in GIO than in primary osteoporosis even in the presence of equal bone mass density. The risk of osteoporotic fractures increases with dose and duration of glucocorticoid therapy, although the loss of bone mass is more prominent within the first three to twelve months after initiation of treatment. Besides glucocorticoid treatment, other factors, such as e.g. the underlying disease, substantially influence the fracture risk. Therefore, a diagnostic screening is mandatory in each case and should include the patient’s history, physical examination, laboratory studies, evaluation of the bone-mass density by dual X-ray absorptiometry and imaging of the spine. Education of the patients and pharmacological prevention are very important, antiresorptive therapy has to be started earlier than in primary osteoporosis and osteoanabolic agents have also been proven to be effective.     

Should perimenopausal women be screened for osteoporosis?

The increasing availability of noninvasive methods for measuring bone mass raises the issue of whether perimenopausal women should routinely have such measurements to identify those at risk for osteoporotic fractures of the hip, wrist, and spine. Although the mortality and morbidity caused by hip fractures would warrant routine screening, measurement of bone mass has uncertain value in assessing the risk for hip fracture. Wrist fractures generally cause only transient disability, and measurement of bone mass may not reliably predict risk. Measurements of bone density of the spine might be better able to assess a woman's risk for vertebral fractures, but the value of screening depends on whether the findings would affect a woman's decision about using estrogen therapy after menopause. Serial measurements of bone mass to estimate a woman's rate of bone loss are relatively imprecise, increase the cost of screening, and have at best a limited role in screening women to assess risk for osteoporotic fractures.     

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.     

What is the role of DXA, QUS and bone markers in fracture prediction, treatment allocation and monitoring?

There is evidence that treatment can decrease the risk of fractures in osteoporotic patients, and screening of these patients is therefore relevant. Diagnosis of osteoporosis is based on the T-score calculated from bone mineral density (BMD) measurements. BMD measurements have been widely used for the management of osteoporosis, and a low BMD is a strong risk factor for fractures. But BMD measurement has several limitations in both diagnosis, prediction of fracture risk, and treatment follow-up. Quantitative ultrasound (QUS) parameters, an alternative to BMD in the assessment of bone, are independent risk factors for osteoporotic fracture. However, the use of QUS cannot be recommended for both allocation and monitoring of treatment. Biochemical markers of bone remodelling can be useful for both prediction of fracture risk and monitoring of treatment if sources of variability are controlled.     

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.     

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.     

Glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.     

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.     

Fracture thresholds in osteoporosis: implications for hormone replacement treatment.

The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade -26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40-49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy.     

Clinical evaluation of osteoporosis and fracture risk in postmenopausal women

For the advanced practice nurse, the goal of identifying postmenopausal women at risk for or diagnosed with osteoporosis is to prevent fractures. The first step to achieving this goal is to assess the patient's risk factors for fracture. The patient assessment, includes obtaining a medical history, performing a physical examination, and ordering a bone mineral density (BMD) test. A combined clinical picture is essential with regard to appropriate pharmacological and nonpharmacological therapy decisions for individual patients. BMD diagnostic categories should not be relied on in the absence of important clinical risk factors when determining an osteoporosis treatment threshold for fracture protection. Advanced practice nurses with expertise in health promotion, disease prevention, and patient education are in a unique position to evaluate the risk of osteoporotic fractures in patients who present for care in primary care settings.     

Fracture risk assessment in Latin America: is Frax™ an adaptable instrument for the region?

Osteoporosis is a generalized disease of bone that increases fracture risk. Multiple factors influence this risk, besides low bone mass. To decrease osteoporotic fractures, those patients who require preventive management should be readily identified. This paper aims to review current information on the use of the fracture risk assessment tool (FRAX™) in Latin America. Bone mineral density measurement is currently the method of reference for evaluating the fracture risk and opting for treatment; but, it misses a notable proportion of individuals who have clinical risk factors for osteoporosis and fractures. FRAX™ was designed to predict the 10-year absolute risk of sustaining a major osteoporotic fracture or a hip fracture. Although data is available for several countries, from Latin America, only Argentina appears in the current version of the tool. Its present use in other Latin American countries is possible with some adaptations based in similarities of epidemiological information of each country with some of the existing databases. The cutoff value beyond which treatment should be initiated needs to be determined, based not only on clinical criteria, but also on economic considerations.     

Effectiveness of bone density measurement for predicting osteoporotic fractures in clinical practice

CONTEXT: Bone density measurement with dual-energy x-ray absorptiometry is widely used for fracture risk assessment. It has not been established that published gradients of fracture risk from study populations can be directly applied to clinical populations. OBJECTIVE: The objective of the study was to assess osteoporotic fracture prediction with dual-energy x-ray absorptiometry in a large clinical cohort. DESIGN: This was a historical cohort study (mean observation period 3.2 +/- 1.5 yr). PATIENTS: The study population was drawn from the population-based database of the Manitoba Bone Density Program. Analyses were limited to women aged 50 yr or older at baseline (n = 16,505). MAIN OUTCOME MEASURE: Each subject's longitudinal health service record was assessed for the presence of nontrauma fracture codes (hip, spine, wrist, and humerus) after bone density testing. Age-adjusted hazard ratios for fracture were derived from Cox proportional hazards models. RESULTS: Site-specific and overall fracture rates were significantly associated with each site of bone density measurement (all P < 0.00001). The 95% confidence intervals overlapped those from a widely cited metaanalysis of fracture prediction from different sites. Although fracture prediction was not significantly different between the three hip measurement sites, each hip site was better than the lumbar spine for predicting overall fractures (nonoverlapping 95% confidence intervals). The manufacturer sd (equivalent to a unit change in T-score) resulted in a significantly smaller gradient of risk for the spine than when the population sd was used. CONCLUSIONS: Bone density measurements are effective for predicting fractures in clinical practice. However, hip measurements were superior to the spine in overall osteoporotic fracture prediction.     

Drug insight: Existing and emerging therapies for osteoporosis

Osteoporosis is a major public health problem that is characterized by microarchitectural deterioration, low bone mass, and increased risk of fractures. Currently, many women and men affected with this disease are not diagnosed or treated. As osteoporosis is often clinically silent, risk-factor assessment and measurement of BMD are needed to identify those who may benefit from osteoporosis therapy. Although adequate daily intake of calcium and vitamin D, and regular weight-bearing exercise are important for skeletal health, they are not adequate treatments for individuals with osteoporosis. Therapies approved for treatment and/or prevention of osteoporosis in the United States include oral bisphosphonates (alendronate, ibandronate and risedronate), calcitonin, estrogens, teriparatide (parathyroid hormone fragment [1-34]), and raloxifene. For most patients, oral bisphosphonates are the treatment of choice, given the large-scale randomized-trial data demonstrating efficacy in fracture reduction, although bisphosphonates that reduce spine and nonspine fractures (e.g. alendronate and risedronate) are preferred. For high-risk patients (those with very low bone density, or with fractures), teriparatide therapy for 2 years should be considered. The treatment paradigm for osteoporosis will evolve further as promising new treatments progress through clinical development.