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.     

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.     

Osteoporosis in postmenopausal women. Therapy options across a wide range of risk for fracture

Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength predisposing individuals to an increased risk of fractures. Fractures related to osteoporosis are frequently associated with chronic pain and decreased quality of life, as well as significant morbidity and mortality. Postmenopausal women are at higher risk for developing osteoporosis and osteoporosis-related fractures. Osteoporosis fractures are commonly asymptomatic, necessitating a need for proactive screening, diagnostic testing, and more importantly, therapeutic intervention that will rapidly reduce the risk of fractures in at-risk patients. Current pharmacologic prevention and treatment options for osteoporosis include antiresorptive therapies (alendronate, risedronate, ibandronate, raloxifene, hormone therapy, and calcitonin) and the anabolic agent teriparatide.     

Management of difficult osteoporosis

Osteoporosis and associated low-impact fractures are common. There is associated morbidity and mortality with low-impact fractures. It is critical to identify which patients would benefit from therapy. General treatment considerations are reviewed. Currently available treatment options are discussed. Certain patient populations pose challenges in the treatment of osteoporosis. An in-depth review of clinically challenging scenarios is presented: Treatment of patients with severe osteoporosis, Treatment of Premenopausal women with low bone density, Treatment of osteoporosis in patients with kidney disease, Treatment of Osteoporosis in patients on glucocorticoid therapy, Treatment of osteoporosis in patients with a fracture.     

The Societal Burden of Osteoporosis

Osteoporosis currently affects 10 million Americans and is responsible for more than 1.5 million fractures annually. The financial burden of osteoporosis is substantial, with annual direct medical costs estimated at 17 to 20 billion dollars. Most of these costs are related to the acute and rehabilitative care following osteoporotic fractures, particularly hip fractures. The societal burden of osteoporosis includes these direct medical costs and the monetary (eg, caregiver time) and nonmonetary costs of poor health. The aging of the US population is expected to increase the prevalence of osteoporosis and the number of osteoporotic fractures. Growth of the older adult population will pose significant challenges to Medicare and Medicaid, which bear most of the cost of osteoporosis. Efforts to address the looming financial burden must focus on reducing the prevalence of osteoporosis and the incidence of costly fragility fractures.     

Management of osteoporosis in patients with gastrointestinal diseases

Osteoporosis is a frequent complication in the course of various gastrointestinal disorders. Since its pathogenesis is complex, and incompletely understood in comparison to the well-known pathomechanism of postmenopausal osteoporosis, adequate management is difficult. We first summarize those therapeutic options which have strong evidence in postmenopausal osteoporosis and, thereafter, we review those in the context of different gastrointestinal diseases. Treatment of the underlying intestinal disorder seems to be most important to normalise altered bone metabolism and to prevent osteoporosis in patients with coeliac disease. In patients with osteoporosis associated with Crohn's disease, various treatment strategies (such as vitamin D, sodium fluoride, bisphosphonates) are discussed. In contrast to postmenopausal osteoporosis, interventional studies in secondary osteoporosis are often limited by the small study population and data about the efficacy of any treatment in prevention of fractures are therefore lacking. Well-conducted, controlled studies with the endpoint of preventing fractures are therefore required to optimise the treatment of osteoporosis in these patients.     

Fractures in the elderly: epidemiology and demography.

Osteoporosis and osteoporosis-related fractures are a major source of both morbidity and cost in the elderly, the fractures that are most commonly associated with osteoporosis being those of the hip, the distal forearm and the vertebrae, although it is believed that most other fractures occurring in the elderly are also related to osteoporosis. In this review, the incidence of all types of fracture is described based on the available literature, and the foreseeable trends resulting from demographic changes are discussed. Emphasis is given to the epidemiology of hip fracture since this is the most serious consequence of osteoporosis. Hip fractures occur all over the world, most currently occurring in Western countries, mainly Europe and the USA, but it is expected that there will be a large increase in the number of hip fractures in other countries because of demographic changes. The incidence of hip fractures increases exponentially with age, resulting in a 1-year incidence of 1% in women aged 80 in Western countries. Most hip fractures occur in women, but this is again partly due to demography, because of the longer life expectancy of women. Wrist fractures occur more often in women and do not show the same increase with age as hip fractures. The incidence reaches a plateau at age 60-70. Vertebral fractures show a modest increase with age and are again more common in women than men. The incidence of all other fractures increases modestly with age Copyright 2000 Harcourt Publishers Ltd.     

Osteoporosis: prophylaxis, diagnostics and therapy according to the guidelines

Osteoporotic fractures are a frequent cause of functional disabilities and loss of quality of life. Preventive measurements need to focus on training of muscle function and coordination, and adequate daily calcium and vitamin D supplementation; furthermore a regular check up for drugs associated with falls and osteoporosis. The German guideline recommends that a specific osteoporosis medication should be initiated in individuals with a 10-year risk for hip and vertebral fractures of 30%. This article presents the current guideline for osteoporosis including the actual updates.     

Update on the epidemiology of osteoporosis

Osteoporosis is a major public health problem that affects the entire aging population. This report provides an update on the epidemiology of osteoporosis and its associated fractures. Published studies from 1997 to the present are highlighted. The current US prevalence estimates for osteoporosis, trends in fracture incidence rates, and latest reports on the morbidity, mortality, and costs attributable to osteoporotic fractures are discussed. Recent advances in our understanding of risk factors associated with osteoporosis and related fractures are reviewed. Special attention is paid to the rapid progress being made in the field of genetics, the growing importance of nutrition, and the new questions being raised as to the influence of hormonal factors on bone mineral density and fracture risk. New studies linking osteoporosis to several other important diseases in women including breast cancer, osteoarthritis, and stroke are also reviewed.     

Incidental vertebral fractures discovered with chest radiography in the emergency department: prevalence, recognition, and osteoporosis management in a cohort of elderly patients

BACKGROUND: Vertebral fractures are common and usually an indication for osteoporosis treatment. However, screening is not recommended, and many fractures go undetected. Our objectives were to determine the utility of chest radiographs for detecting previously unrecognized vertebral fractures; document rates of recognition; and evaluate osteoporosis treatments. METHODS: In 2001, we conducted a cohort study in a random sample of 500 patients older than 60 years who presented to our emergency department and underwent chest radiography for any indication. The primary outcome was prevalence of moderate-to-severe vertebral fractures determined by independent radiograph review using validated semiquantitative techniques. Secondary outcomes were rates of fracture recognition according to official radiologists' reports and rates of osteoporosis diagnosis and treatment. We conducted multivariable regression analyses to determine correlates of study-defined and officially reported fractures. RESULTS: We excluded 36 patients with inadequate radiographs and 5 for other reasons. Mean age was 75.2 years; 47% were women; and 80% were white. The prevalence of moderate-to-severe vertebral fractures according to independent review was 72 (16%) of 459; 29 (40%) of these fractures were not recorded in the official radiologists' report (kappa = 0.64; 95% confidence interval [CI], 0.53-0.75). A history of osteoporosis was the only independent correlate of having a vertebral fracture identified by independent review (adjusted odds ratio [OR], 2.18; 95% CI, 1.14-4.17) or by official report (adjusted OR, 4.97; 95% CI, 0.95-25.86). Of the 72 patients with fractures, only 18 (25%) had histories of osteoporosis or received osteoporosis medications. CONCLUSIONS: One in 6 elderly patients who underwent chest radiography in our emergency department had clinically important vertebral fractures. Nevertheless, only 43 (60%) of these fractures were reported, and only 25% of patients with fractures received a diagnosis of or treatment for osteoporosis.     

Osteoporose

Osteoporotic fractures are a frequent cause of functional disabilities and loss of quality of life. Preventive measurements need to focus on training of muscle function and coordination, and adequate daily calcium and vitamin?D supplementation; furthermore a regular check up for drugs associated with falls and osteoporosis. The German guideline recommends that a specific osteoporosis medication should be initiated in individuals with a 10-year risk for hip and vertebral fractures of 30%. This article presents the current guideline for osteoporosis including the actual updates.     

Osteoporosis in men

With the aging of the population, there is a growing recognition that osteoporosis and fractures in men are a significant public health problem, and both hip and vertebral fractures are associated with increased morbidity and mortality in men. Osteoporosis in men is a heterogeneous clinical entity: whereas most men experience bone loss with aging, some men develop osteoporosis at a relatively young age, often for unexplained reasons (idiopathic osteoporosis). Declining sex steroid levels and other hormonal changes likely contribute to age-related bone loss, as do impairments in osteoblast number and/or activity. Secondary causes of osteoporosis also play a significant role in pathogenesis. Although there is ongoing controversy regarding whether osteoporosis in men should be diagnosed based on female- or male-specific reference ranges (because some evidence indicates that the risk of fracture is similar in women and men for a given level of bone mineral density), a diagnosis of osteoporosis in men is generally made based on male-specific reference ranges. Treatment consists both of nonpharmacological (lifestyle factors, calcium and vitamin D supplementation) and pharmacological (most commonly bisphosphonates or PTH) approaches, with efficacy similar to that seen in women. Increasing awareness of osteoporosis in men among physicians and the lay public is critical for the prevention of fractures in our aging male population.     

Vitamin K and bone quality

Dietary vitamin K intakes becomes reduced with aging. Low vitamin K intakes are associated with an increased incidence of hip fractures and an increase of under carboxylated osteocalcin in elderly men and women. The increase of under carboxylated osteocalcin is a risk factor for fractures in osteoporosis. Vitamin K2 treatment is effective for the prevention of fractures, but not for the increase of bone mineral density in osteoporosis. Vitamin K2 administration could be a potential treatment to improve the bone quality.     

Treatment of osteoporosis with bisphosphonates

Bisphosphonates are safe and effective agents for treatment and prevention of osteoporosis. Alendronate and risedronate are the best studied of all agents for osteoporosis in terms of efficacy and safety. They increase bone mass. In patients who have established osteoporosis, they reduce the risk of vertebral fractures. They are the only agents shown in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. They are approved by the US FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for management of glucocorticoid-induced bone loss. Other bisphosphonates (e.g., etidronate for oral use, pamidronate for intravenous infusion) are also available and can be used off-label for patients who cannot tolerate approved agents. Bisphosphonates combined with estrogen produce greater gains in bone mass compared with either agent used alone; whether there is a greater benefit of combination therapy on fracture risk is not clear. Combining a bisphosphonate with raloxifene or calcitonin is probably safe, although data on effectiveness are lacking.     

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.     

Does the french general practitioner correctly investigate and treat osteoporosis?

In our region, more than half the patients with osteoporosis are investigated and treated by general practitioners. We carried out two surveys to discover whether the diagnosis and treatment of osteoporosis were correctly carried out by general practitioners in the Midi-Pyrénées region. The first survey concerned 85 patients who had been diagnosed with osteoporosis by their general practitioner. These patients were being seen for the first time in a hospital or private practice setting by a rheumatologist who completed a questionnaire based solely on the history taken from the patient and the records in the patient's possession. For the second survey, 200 general practitioners who had referred patients to the rheumatology department were sent a questionnaire on their management of osteoporosis. Fifty-two physicians completed and returned the questionnaire. More than half the general practitioners started treatment of osteoporosis without fractures on the basis of standard spinal X-rays where the radiologist suggested bone mineral loss. The initial biological investigation was correctly carried out by only 6% of physicians. Treatment was correctly prescribed in only 34% of cases of osteoporosis with fractures, 50% of osteoporosis without fractures and 50% of senile cortical osteoporosis.     

COPD, bone metabolism, and osteoporosis

COPD and osteoporosis are strongly associated because of common risk factors such as age, smoking, and inactivity. In addition, COPD-related systemic inflammation, vitamin D deficiency, and the use of systemic corticosteroids enhance ongoing bone destruction. Osteoporosis, in turn, may cause fragility fractures, which further impair mobility and increase morbidity and mortality. Vertebral compression fractures and rib cage fractures in patients with COPD may also reduce pulmonary function or enhance exacerbations. Early prevention and treatment of osteoporosis in COPD is, therefore, important and should be based on integrated risk assessment tools such as FRAX, which take bone mineral density, history of fragility fractures, and population-specific clinical factors into account. As long as intervention studies focusing on the bone in COPD are lacking, a more rigorous application of existing treatment guidelines of osteoporosis in general is mandatory.     

Prevention of incident fractures in patients with prevalent fragility fractures: Current and future approaches

Fragility fractures are a significant, independent risk factor for new fractures, but treatment uptake in subjects with prevalent fractures is disappointing. We addressed the question of the efficacy of pharmacological interventions in reducing the risk of incident fractures in patients with prevalent fragility fractures. For this, we reviewed randomised controlled trials (RCTs), pre-planned and post-hoc analyses of RCTs of approved agents for the treatment of osteoporosis. Results showed that a number of agents decrease the risk of incident vertebral and nonvertebral fractures in subjects with prevalent vertebral fractures, justifying the recommendation of treating such patients independently of the level of bone mineral density (BMD). By contrast, the evidence of antifracture efficacy of these agents in patients with prevalent nonvertebral fractures is limited. Advances in our understanding of the regulation of bone metabolism at the molecular level have identified targets for the development of new therapeutics for osteoporosis, some of which are currently in phase 3 clinical development.     

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.