Osteoporosis is a reduction in bone mineral density (BMD), loss of bone strength, and deterioration of the skeletal microarchitecture resulting in fragile bones and fractures (hip, spine, wrist). There are two types of bone in the human skeleton (cortical and trabecular). Cortical bone (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 (cancellous bone) is porous (sponge like). This type of bone is soft, weak, and flexible; 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 construction and mineralization (with calcium and phosphorous) of bone. Osteoclasts break down (or resorp) bone to form cavities within the tissue. 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. In a young adult, bone remodeling is stable as new bone is generated to remove and replace damaged bone. Peak bone mass will be achieved between the ages of 25 and 35. 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 loss 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 nuclear factor-κ B ligand. This pathway induces 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
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 48-1).
Conditions: endocrine (Cushing disease), gastrointestinal (inflammatory bowel disease), rheumatologic (rheumatoid arthritis)
TABLE 48-1Medications Associated With Bone Loss and Fracture Risk |Favorite Table|Download (.pdf) TABLE 48-1Medications Associated With Bone Loss and Fracture Risk
|Medications ||Comments |
|Anticonvulsant therapy (phenytoin, carbamazepine, phenobarbital, valproic acid) ||↓ BMD and ↑ fracture risk; increased vitamin D metabolism leading to low 25(OH) vitamin D concentrations |
|Aromatase inhibitors (eg, letrozole, anastrozole) ||↓ BMD and ↑ fracture risk; reduced estrogen concentrations |
|Furosemide ||↑ Fracture risk; increased calcium renal elimination |
|Glucocorticoids (chronic oral therapy) ||↓ BMD and ↑ fracture risk; dose and duration dependent; see Special Populations section |
|Gonadotropin-releasing hormone agonists or analogs (eg, leuprolide, goserelin) ||↓ BMD and ↑ fracture risk; decreased sex hormone production |
|Heparin (unfractionated) or low-molecular-weight heparin ||↓ BMD and ↑ fracture risk (unfractionated >>> low molecular weight) with long-term use ...|