Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged > 65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.     

Insufficiency fractures of the sacrum: a cause of low back pain after lung transplantation

Insufficiency fractures of the sacrum were diagnosed during the first year after successful transplantation in four (5.6%) of 71 lung and heart-lung transplant recipients. Each patient had development of low back pain after minor or no trauma; all had osteoporosis. In each instance, plain radiographs failed to demonstrate the fracture, and the diagnosis was established by radionuclide bone scanning that demonstrated the characteristic "butterfly" (bilateral sacral fracture) or "half-butterfly" appearance (unilateral sacral fracture). Sacral insufficiency fractures, a significant cause of low back pain in lung transplant recipients, may be underdiagnosed in this population because routine radiographs do not usually reveal the fracture; bone scanning is the preferred diagnostic modality.     

Age-related bone loss and senile osteoporosis: evidence for both secondary hyperparathyroidism and skeletal growth factor deficiency in the elderly

Aging is characterized by a decrease in bone volume, implying that net bone resorption exceeds net bone formation. This age-related bone loss can be regarded as the main determinant of hip fracture risk in the elderly. In the concept of senile osteoporosis, a key role has been attributed to vitamin D deficiency. Lack of vitamin D activity may affect femoral strength through impaired mineralization as well as through a hyperparathyroidism-mediated increase in bone resorption. In addition to vitamin D-related mechanisms, recent evidence has indicated a decline in the skeletal content of anabolic growth factors--such as insulin-like growth factor-I (IGF-I)--in femoral (cortical) bone, suggesting that skeletal growth factor deficiency may contribute to the age-related bone loss in the proximal femur as well. It is tempting to speculate that skeletal IGF-I loss might, at least partially, be accounted for by growth hormone deficiency. However, critical evidence does not yet support the concept that the decreased activity of the growth hormone-IGF-I-axis alters bone remodeling, and the extent to which serum concentrations of growth factors are reflective of skeletal activity remains to be clarified.     

A simple procedure that increases the specificity of the activated protein C resistance test in samples containing antiphospholipid antibodies

This article suggests classifying "osteoporoses" by their biomechanical pathogenesis instead of by their severity or their accompanying medical conditions. (A) In a "true osteoporosis," bone fragility would increase to such an extent that normal physical activity would cause spontaneous fractures and/or a bone pain syndrome, mainly affecting the spine; however, falls could also cause extremity bone fractures. (B) In a "physiologic osteopenia," reduced bone strength and "mass" would fit correspondingly reduced physical activities and muscle strength so well that fractures would not happen without falls or other injuries. Those fractures would affect extremity bones more than the spine. (C) In "combination states," features of (A) and (B) would combine variably. (D) "Transient osteopenias" would occur while serious injuries heal. After healing, transient osteopenias usually resolve without treatment, and fractures occur only from injuries. While an osteopenia's severity usually affects the risk of fracture, its pathogenesis could strongly affect the treatment needed for prevention or cure.     

Differential osteoporosis diagnosis in the woman

Bone mineral density of a woman in the second half of her life depends on the amount of bone made during growth and its subsequent rate of loss. Although the rate of bone loss did receive more attention in the study of pathogenesis of osteoporosis, it is becoming increasingly clear that insufficient accumulation of skeletal mass by young adulthood predisposes a person to low bone mass and subsequently to fractures later in life as age related and menopause-related bone loss ensue. In this article we 1) explain the role of inadequate peak bone mass as a major risk factor for osteoporosis and 2) give an overview of factors leading to osteoporosis by decreasing bone mass. Special emphasis has been put on iatrogenic osteoporosis which is frequently neglected because of the fact that the responsible agents often are not known as to be deleterious to the skeleton: among others, glucocorticoids, thyroid hormones and antiepileptics adversely affect bone.     

Detecting osteoporosis. Beyond the history and physical examination

A number of developments are contributing to clinicians' understanding of osteoporosis as a clinical continuum characterized by low bone mass and increased risk of fractures rather than as a disease characterized by fragility fractures. With improved capability for accurate measurement of bone mass, the prevalence of this disease has increased to include at least 25 million Americans. The responsibility of primary care physicians to detect and treat osteoporosis has increased accordingly. Parents should be counseled regarding their children's diet and lifestyle to optimize peak adult bone mass and ensure adequate dietary calcium intake. Adults should be counseled to minimize behaviors that result in accelerated bone loss (e.g., smoking, alcohol use, anorexia, bulimia). Physicians need to be aware of the serious potential complications of osteoporosis and offer counseling to menopausal women about the disease and the benefits and risks of hormone replacement and estrogen replacement therapy. Physicians should be familiar with technologies available in their community for measuring bone mass and recognize the need to consider prescribing pharmacologic and nonpharmacologic therapies for patients with low bone mass or osteoporosis. Physicians also can educate caregivers about prevention of falls and fractures in elderly patients who are unsteady on their feet. Improved technologies for bone mass measurement and fracture risk assessment, as well as expanded options for treatment and prevention of osteoporosis, are likely to become available within the next 5 to 10 years, thereby increasing the wisdom of early detection and treatment of osteoporosis.     

Secondary amenorrhea leading to osteoporosis: incidence and prevention

Osteoporosis is widely accepted as a "female disease" occurring primarily in postmenopausal women. The fact that this disease can affect premenopausal women experiencing menstrual dysfunction is less commonly known. Amenorrhea decreases bone density at an age when bone formation should still be occurring. The implications of this failure to attain sufficient bone density during the formative years are frightening. The adverse effects on skeletal strength may lead to devastating outcomes in this subgroup of women, either now or in the future. This article reviews causes, risk factors, and treatments associated with both osteoporosis and amenorrhea. Three causes of secondary amenorrhea are discussed in detail: rigorous physical training, anorexia nervosa, and use of the contraceptive agent medroxyprogesterone acetate injection. A review of the literature is presented in order to establish the link between amenorrhea and osteoporosis. A great many young women may be unknowingly placing themselves at risk for developing osteoporosis. This article includes interventions that may decrease this risk and improve quality of life.     

Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis

BACKGROUND: Small increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed. METHODS: We did a 3-year randomised controlled trial to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25 micrograms daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n = 17). The controls were women taking hormone-replacement therapy only (n = 17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints. FINDINGS: Patients taking hormone-replacement therapy and PTH (1-34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13.0% (p < 0.001); 2.7% at the hip (p = 0.05); and 8.0% in total-body bone mineral (p = 0.002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p = 0.04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment. INTERPRETATION: We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.     

The skeleton after spinal cord injury. Part 1. Theoretical aspects

Sublesional osteoporosis occurs after acute spinal cord injury (SCI), preferentially weakening the skeleton below the level of the neurological lesion. Although its pathogenesis is unclear, it resembles post-menopausal, high turnover osteoporosis. Physical and pharmacologic therapies are currently being tested for their ability to prevent early loss and restore lost bone. Although treatment strategies hold promise, preservation of skeletal strength after injury may ultimately rest on lifestyle decisions made early in life. If skeletal strength is to be maintained after SCI, ways must be found to optimize skeletal strength prior to injury, arrest early losses, and stabilize, if not restore, lost bone over time.     

Vacuum phenomena in the sacroiliac joints and in association with sacral insufficiency fractures. Incidence and significance

STUDY DESIGN: The computed tomography scans of two groups of patients of similar age and sex, with and without sacral insufficiency fractures, respectively, were assessed retrospectively. OBJECTIVES: To determine the incidence of sacroiliac joint vacuum phenomena in individuals with and without sacral insufficiency fractures and to evaluate a possible association between vacuum phenomena and sacral insufficiency fractures. SUMMARY OF BACKGROUND DATA: The occurrence of vacuum phenomena is well recognized in the vertebra, but not in the sacroiliac joint. Gas foci in sacral insufficiency fractures recently has been reported. It has been suggested that the presence of vacuum phenomena may aid in the diagnosis of these fractures. METHODS: The computed tomography scans of 28 female patients with sacral insufficiency fractures and of 60 age- and sex-matched control individuals were evaluated. RESULTS: In the group with sacral insufficiency fractures, vacuum phenomena were detected in 69.2% of patients and in 63.5% of sacroiliac joints, with sacroiliac joint-related osteophytes found in 19.2% of patients. Very similar incidences were demonstrated in the control group. There was no correlation between sacroiliac joint osteophytes and vacuum phenomena in either group. The vacuum phenomenon was detected within the sacral insufficiency fracture in only one patient, in whom the fracture communicated with the adjacent sacroiliac joint. CONCLUSION: Vacuum phenomena are frequently found in the sacroiliac joints of elderly women, and their presence is of no diagnostic significance when demonstrated in patients with sacral insufficiency fractures.     

Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory

Osteoporotic fractures, and in particular, hip fractures result in significant morbidity and mortality. Low bone mass is the main risk factor of enhanced bone fragility, resulting in an increased risk for hip fracture. Bone density of osteoporotic women with and without hip fractures show a considerable overlap. Therefore, other bone-independent factors also play an important role for the development of hip- and other osteoporotic fractures. One other important factor is falling. In 90% of hip fractures falling was involved [10-15], but only 5% or less of these falls resulted in a subsequent fracture. The view that adequate exercise is beneficial for skeletal health of children and for prevention and treatment of osteoporosis in adults is supported primarily by two lines of evidence: longitudinal and cross-sectional trials in children and young adult athletes showing a significant increase of muscle- and bone mass after strenuous (children) or chronic exercise (athletes) as compared to normally active (children) or sedentary control subjects. What are the potential benefits and limits of specific exercise programs with respect to bone mass, prevention of falls and fractures? In this review these questions are discussed and a specific exercise program in osteoporotic patients with fractures is delineated.     

Can we prevent fractures?

The primary aim of any intervention in osteoporosis is the prevention of fractures in individuals who have not yet fractured or the prevention of the progression of the disease in individuals with fragility fractures. There is currently insufficient evidence to recommend either a population-based prevention strategy or a strategy based on general screening with treatment of those individuals identified at high risk. Identification of subjects with strong clinical risk factors for osteoporotic fractures with subsequent measurement or not of bone mineral density as well as those with fragility fractures constitute at present the most rational approach to fracture prevention. Current measures to prevent osteoporotic fractures aim mainly at influencing bone mass and bone turnover and reducing the risk and impact of falls. Interventions that can reduce effectively the frequency of osteoporotic fractures in subjects at risk are available and new or alternative interventions are being developed. Issues related to the impact of these interventions on public health and health economics need to be addressed and methods to calculate the clinical outcomes in a way allowing comparison with outcomes of interventions in other common diseases should be developed.     

Glucocorticoid-induced osteoporosis: prevention and treatment

Glucocorticoid excess carries the risk of inducing secondary osteoporosis. In endogenous Cushing's syndrome, osteoporosis may be the presenting symptom of the underlying disease. Bone loss may reverse after the condition is cured, but often active treatment of established osteoporosis is necessary. In long-term glucocorticoid treatment at therapeutic doses, bone loss is likely and should be prevented; if prevention is ineffective, treatment is necessary. Hypercortisolism impairs calcium homeostasis and bone metabolism in a complex, multifactorial way: Glucocorticoids diminish calcium absorption and increase renal calcium excretion; this negative calcium balance leads to secondary hyperparathyroidism and osteoclast activation. Osteoblast activity is directly impaired by glucocorticoids, which lower activity of the gonadal hormone axis so that hypogonadism also contributes to bone loss. Glucocorticoids lead to muscle atrophy and decreased muscle strength with negative consequences for bone formation. For prevention and treatment, two different strategies have been used. The pathophysiological approach substitutes calcium and vitamin D in the first step; if bone loss nevertheless continues, bone formation is stimulated by fluorides. The alternative pharmaco-dynamic approach uses antiresorptives-calcitonin or, for preference, bisphosphonates. Clinically it is mandatory to monitor all patients in whom glucocorticoids are used (e.g., organ transplant recipients) before and after the initiation of treatment to stabilize bone metabolism as early as possible.     

Bone densitometry: patients receiving prolonged steroid therapy

Bone mass loss and osteoporosis are associated with various conditions, such as asymptomatic primary hyperparathyroidism, and treatments, such as prolonged steroid therapy. Bone densitometry is used to measure bone mass density to determine the degree of osteoporosis and to estimate fracture risk. Bone densitometers measure the radiation absorption by the skeleton to determine bone mass of the peripheral, axial, and total skeleton. Common techniques include single-photon absorptiometry (SPA) of the forearm and heel, dual-photon (DPA) and dual-energy x-ray absorptiometry (DXA) of the spine and hip, quantitative computed tomography (QCT) of the spine or forearm, and radiographic absorptiometry (RA) of the hand. Part I of this report addresses important technical considerations of bone densitometers, including radiation dose, site selection, and accuracy and precision, as well as cost and charges. Part II evaluates the clinical utility of bone densitometry in the management of patients receiving prolonged steroid therapy. Steroids have broad effects on both immune and inflammatory processes and have been used to treat a wide variety of immunologically mediated diseases. Osteoporosis and vertebral compression fractures have been considered major complications of prolonged steroid therapy. Bone loss is also a direct result of many of the diseases treated with steroids. Issues addressed are the type and extent of bone loss associated with steroid therapy, risk for fracture, whether steroid dose reduction or alternative therapy is an option, and whether osteoporosis associated with prolonged steroid use can be prevented or treated. The other assessments in this series address the clinical utility of bone densitometry for patients with: asymptomatic primary hyperparathyroidism, end-stage renal disease, vertebral abnormalities, and estrogen-deficient women.     

Fibromyalgia syndrome and disability: the neurogenic model

Office-based physicians can now use ultrasonography of the heel to screen for osteoporosis and estimate the risk of fractures. In treating osteoporosis, alendronate has been shown to increase bone mineral density and to decrease the incidence of fractures.     

Calcium metabolism, osteoporosis and essential fatty acids: a review

Essential fatty acid (EFA)-deficient animals develop severe osteoporosis coupled with increased renal and arterial calcification. This picture is similar to that seen in osteoporosis in the elderly, where the loss of bone calcium is associated with ectopic calcification of other tissues, particularly the arteries and the kidneys. Recent mortality studies indicate that the ectopic calcification may be considerably more dangerous than the osteoporosis itself, since the great majority of excess deaths in women with osteoporosis are vascular and unrelated to fractures or other bone abnormalities. EFAs have now been shown to increase calcium absorption from the gut, in part by enhancing the effects of vitamin D, to reduce urinary excretion of calcium, to increase calcium deposition in bone and improve bone strength and to enhance the synthesis of bone collagen. These desirable actions are associated with reduced ectopic calcification. The interaction between EFA and calcium metabolism deserves further investigation since it may offer novel approaches to osteoporosis and also to the ectopic calcification associated with osteoporosis which seems to be responsible for so many deaths.     

Bone mass and ageing

Bone can be divided into two kinds of tissue, cortical and trabecular bone. The skeleton comprises approximately 80% cortical bone, mainly in peripheral bones, and 20% trabecular bone, mainly in the axial skeleton. Bone density increases with skeletal growth to a peak in late adolescence or early adulthood. Bone loss subsequently occurs with ageing in both sexes, and in females accelerated loss occurs at the menopause. The risk of osteoporotic fracture in later life is the result of peak bone mass achieved at skeletal maturity and subsequent age-related and postmenopausal bone loss. Peak bone mass is largely genetically determined but is also influenced by environmental factors such as dietary calcium and physical activity. Bone loss with ageing occurs at different rates and different times in different skeletal sites. Femoral neck bone loss probably occurs in a linear fashion throughout life from early adulthood but may be accelerated at the menopause. Spinal bone loss may commence before the menopause but is rapidly increased in the immediate postmenopausal years. Bone strength is directly related to bone density, but the loading force is also relevant to risk of fracture.     

Effects of melatonin on lipid peroxidation induced by oxygen radicals

Osteoporosis is characterized by reduced bone mass and a deterioration of bone structure which results in an increased fracture risk. The purpose of this review is to evaluate structure analysis techniques in the diagnosis of osteoporosis. Several imaging techniques were applied to analyze trabecular bone, such as conventional radiography, high-resolution computed tomography (HR-CT) and high-resolution magnetic resonance imaging (HR-MRI). The best results were obtained using high-resolution tomographic techniques. The highest spatial resolutions in vivo were achieved using HR-MRI. These studies show that texture parameters and bone mineral density predict bone strength and osteoporotic fractures in a complementary fashion. Combining both techniques yields the best results in the diagnosis of osteoporosis.     

Stress fractures of the femoral neck

Stress fractures of the femoral neck are uncommon injuries. In general these injuries are seen in two distinct populations: (1) young, healthy, active individuals such as recreational runners, endurance athletes, or military recruits; and (2) the elderly who have osteoporosis. Stress fractures can be classified as either fatigue or insufficiency fractures and result from untoward cyclic loading or impaired bone quality. The key to treatment is early diagnosis, which may require scintigraphy or magnetic resonance imaging. Nondisplaced compression type stress fractures can be treated nonoperatively with protected weight-bearing and frequent radiographic followup. Tension type stress fractures should be stabilized internally to prevent the adverse consequences of fracture displacement.     

Osteoporosis in rheumatoid arthritis

In cases of rheumatoid arthritis, osteoporosis may be local or general. The aetiology is multifactorial. Reduced bodily function, synovial inflammation, steroids and menopause are important risk factors. Studies have shown that, in cases of primary osteoporosis, bone mineral density measurements in the distal radius may predict risk of fracture at other sites, such as the neck of the femur and the dorsal vertebrae. Such a connection is not found for rheumatoid arthritis. Bone density measurements in the distal radius may overestimate the risk of fractures due to localised periarticular osteoporosis. Overall bone quality is assumed to be poorer, however, in patients with rheumatoid arthritis, leading to higher risk of fracture than the bone mineral density measurements seem to show. Data are lacking on the effect of antiresorptive drugs on this condition. Treatment with oestrogen and the bisphosphonate pamidronate has been shown to increase bone mineral density. Data are lacking on fractures. As shown in the case of primary osteoporosis, decreased risk of fracture is to be expected also in patients with secondary osteoporosis.