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Osteoporosis is a reduction in bone mineral density (BMD), loss of bone strength, and deterioration of the skeletal microarchitecture resulting in fragile bones. Due to a decrease in bone strength and loss of bone quality, there is an increased risk of fractures, particularly of the hip, spine, and wrist. Women have a higher risk of an osteoporotic fracture per year, compared to men; however, men have a higher mortality associated with an osteoporotic fracture. There are two types of bone in the human skeleton—cortical and trabecular. Cortical bone, or compact bone, is a dense, strong bone and forms the outer shell found in long and flat bones. Cortical bone accounts for bone strength and is 80% of the weight for the human skeleton. Trabecular bone, also known as cancellous bone, is porous (ie, sponge-like). This type of bone is soft, weak, and flexible and, therefore, susceptible to fracture. Trabecular bone is on interior surfaces of long bones, vertebrae, and distal forearms.

Bone remodeling is controlled by osteoblasts and osteoclasts. Osteoblasts are responsible for the formation and mineralization (with calcium and phosphorous) of bone. Osteoclasts break down bone to form cavities within the tissue (ie, resorption). As bone formation exceeds resorption, the overall increase in bone mass can be achieved as 90% of bone mass can be attained by the age of 18 or 20 years, with peak bone mass achieved by the age of 25 to 35 years. In a young adult, bone remodeling is stable as new bone is generated to remove and replace damaged bone. As a person ages, there will be an imbalance in the remodeling process—driven by osteoclasts and its resorptive properties. For example, a female could lose 3% to 5% of bone mass each year during the first 5 to 7 years of menopause. Another mechanism for the development of osteoporosis involves receptor activator of nuclear factor-kappa B (RANK) ligand. RANK-L is secreted by osteoblasts and will bind to the RANK receptor on osteoclasts, therefore, inducing bone resorption by promoting the differentiation, formation, and survival of osteoclasts.

Osteoporosis is classified as primary and secondary. The classification includes:

  • Primary: No known cause, but found most often in postmenopausal women and aging men.

    • Type I: Postmenopausal osteoporosis due to differentiation, formation, and prolonged survival of osteoclasts.

    • Type II: Age-related osteoporosis due to reduction in osteoblasts and changes in other contributing factors (ie, hormones, calcium, vitamin D), as well as decreased testosterone in men.

  • Secondary: Known cause from medication or condition.

    • Medications: Anticoagulants, anticonvulsants, aromatase inhibitors, barbiturates, chemotherapeutic agents, depot medroxyprogesterone, glucocorticoids, gonadotropin-releasing agonists, lithium, proton pump inhibitors, and thiazolidinediones (Table 49-1).

      • Glucocorticoid-induced osteoporosis is the most common type of secondary osteoporosis. It occurs due to apoptosis of osteoblasts and osteocytes, as well as an increase in RANK-L.

    • Conditions: Endocrine (Cushing disease), gastrointestinal (GI) (inflammatory bowel disease), and rheumatologic (rheumatoid arthritis).

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