107 - Metabolic Bone Disease

Abstract

Osteoporosis is a disease defined by low bone density and deterioration of microarchitecture, which reduces bone strength and increases fracture risk. Major clinical risk factors for osteoporotic fractures include older age, low weight, family history of hip fracture, fracture occurring after age 50 years, glucocorticoid use, and inability to rise from a chair without assistance. More than 50% of osteoporosis in men results from secondary causes. Post-menopausal and age-related bone loss results from an uncoupling of bone remodeling such that bone resorption is greater than bone formation, resulting in a net loss of bone. Evaluation for risk of osteoporotic fractures with the Fracture Assessment Index (FRAX) for post-menopausal women and for men is critical to determine which people have a 10-year fracture risk (for the hip and major osteoporotic fracture sites) that is high enough to warrant treatment. Treatment of high-turnover osteoporosis resulting from estrogen deficiency with anti-resorptive agents (e.g., estrogen, raloxifene, and bisphosphonates [alendronate, risedronate, zoledronic acid, ibandronate, and denosumab]) and anabolic agents (recombinant human parathyroid hormone 1-34, PTHrP analogue, and an antibody against sclerostin) can reduce incident vertebral fractures. Treatment for osteoporosis with bisphosphonates should continue for 3 to 5 years, after which, if the bone mineral density T-score is greater than −2, the subject has not sustained a fracture, and the overall risk of fracture is low, the treatment can be discontinued and the patient can be observed. Parathyroid hormone–related compounds (PTH and PTHrP) and an antibody to sclerostin increase osteoblast maturation and lifespan, increase trabecular bone mass and cortical thickness, improve bone strength, and decrease fractures. Anti-resorptive therapy is necessary after a full course of PTH or anti-sclerostin antibody to maintain newly formed bone mass. Glucocorticoid-induced reduction in bone strength results from increased osteoclast activity and reduced osteoblast activity and is most severe in the first 6 months of therapy. Bisphosphonate treatment can prevent fractures, and treatment with hPTH (1-34) can reverse glucocorticoid-induced osteoporosis and reduce incident fractures. Aromatase inhibitors reduce levels of serum estrogen and result in rapid bone loss in post-menopausal women undergoing adjuvant breast cancer therapy. Gonadotropin-releasing hormone agonists decrease testosterone and estrogen levels and cause bone loss in men being treated for prostate cancer.