_______________________________________________________ Osteoporosis: Diagnosis and Management
Men also are affected by osteoporosis, although they represent only about 20% of the cases [5]. Part of the reason for this may be that this population has not been studied as frequently as postmenopausal women. In fact, the number of men with osteoporosis has not been clearly quantified, and the WHO bone mineral density cut-offs are not necessarily applicable. In general, men have greater peak bone mass and greater BMD [3]. As a result, they usually present with fractures 10 years later than women [25]. Sex-specific T-scores are available, but the appropriate cut-offs have not been definitively determined; more research is needed. Up to 20% of hip fractures and 20% of vertebral fractures occur in men. Of note, mortality associated with hip fractures in men is nearly 50% higher than in women [5; 25]. AGE All patients lose bone mass as they age. Consequently, the incidence of osteoporosis increases with age. Age does predict fracture risk independent of BMD; however, osteoporosis is not an inevitable consequence of aging [11]. For patients with the same T-score, there is still a significant difference in fracture risk across age groups. For example, a woman 80 years of age with a T-score of -2.0 has a greater risk of hip fracture over 10 years than does a woman 70 years of age with the same T-score. This difference is likely attributable to decreasing bone quality as well as other factors, including unsteadiness, decreasing muscle strength, and comorbidities that occur with aging [24]. COSTS Osteoporotic fractures account for an estimated $19 billion in healthcare expenditures annually [2]. These costs are expected to rise to $25.3 billion by 2025 [2]. Osteoporosis causes nearly 300,000 hip fractures, 547,000 vertebral (spine) fractures, 397,000 wrist fractures, and almost 675,000 other fractures each year. Annual medical costs related to hip fractures alone are expected to double or triple by 2040 [26]. Osteoporosis results in more than 432,000 hospital admissions, 2.5 million physician visits, and 180,000 nursing home admissions annually [20]. Notably, statistics relating to cost are most often based on treatment and hospital costs, thereby underestimating the true total costs associated with this disease [27]. The indirect costs of osteoporosis have not yet been accurately ascertained, but the decreased productivity, lost wages, and psychologic and social factors associated with osteoporosis and related fractures are substantial. For example, hip fracture patients have demonstrated a lower baseline health-related quality of life and a prolonged and significant deterioration in health-related quality of life following hip fracture [28; 29]. The costs of osteoporosis should also encompass the effects on people around the patient. The caregiver and close family members also suffer decreased productivity due to the emotional and physical strain associated with the high level of care required for these patients.
PATHOPHYSIOLOGY The development of osteoporosis results from defective bone remodeling. Normally, bone is under a continuous remodeling process of formation by osteoblasts and resorption by osteoclasts. When the resorption exceeds the formation (either due to decreased formation, increased resorption, or combination of the two), bone density decreases, bone quality deteriorates, and the patient develops osteopenia or osteoporosis. Osteoblasts are formed from the same precursors as fibroblasts, the cells that produce collagen. They ultimately are responsible for the formation of osteoid, or bone matrix. Mineralization of this osteoid matrix produces bone, and the osteoblasts that remain following mineralization become the osteocytes, the functioning bone cells. Osteoblasts respond to a variety of humoral factors, such as estrogen, vitamin D, cytokines, and the various growth factors that stimulate bone formation. Osteoclasts act in opposition to osteoblasts and, interestingly, result from a line of hematopoietic cells. Like osteoblasts, they respond to many signals that are necessary for cell development. Because osteoclasts are formed from the same line as many blood cells, they also respond to granulocyte colony-stimulating factor and a wide range of interleukins. They are inhibited in their differentiation by the protein osteoprotegerin. Osteoclasts attach to endosteal bone and secrete acid to dissolve calcium crystals. Enzymes like metalloproteinases then act to break down the protein matrix and the osteoclast undergoes apoptosis. The breakdown materials from this protein degradation may be measured as possible markers of bone resorption. The imbalance of osteoclastic and osteoblastic activity may be caused by several age- and disease-related factors. There is some difference of opinion about how to classify the categories of osteoporosis; however, many authorities utilize three main categories: primary osteoporosis, postmenopausal osteoporosis (generally included in the category of primary osteoporosis), and secondary osteoporosis [23]. PRIMARY OSTEOPOROSIS Primary, age-related, or low-turnover osteoporosis results from decreasing bone mineral density and bone quality with age. Normal aging processes decrease gonadal function, and physical activity is usually less strenuous. Everyone reaches a peak bone mass around the third decade of life, usually between 25 to 30 years of age. The maximum BMD achieved by any individual depends upon genetic factors, nutrition, endocrine status, and physical activity. Bone density then gradually decreases as the individual ages. This primary type of osteoporosis is due to decreased bone formation without declining osteoclastic action. The molecular changes that lead to this type of osteoporosis are not clear at this time; however, micrographs of bone show loss of trabecular plates in cancellous bone [20].
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