TY - JOUR
T1 - The Pathophysiology and Treatment of Osteoporosis
AU - Drake, Matthew T.
AU - Clarke, Bart L.
AU - Lewiecki, E. Michael
N1 - Publisher Copyright:
© 2015 Elsevier HS Journals,Inc. All rights reserved.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Purpose The objectives of this article are to review the pathophysiology of bone loss associated with aging and to review current pharmacologic approaches for the treatment of osteoporosis. Methods A literature search with PubMed was performed with the terms osteoporosis and pathophysiology and osteoporosis and treatment and limited to studies written in English that were published within the preceding 10 years. Given the large number of studies identified, we selectively reviewed those studies that contained primary data related to osteoporosis pathophysiology or osteoporosis pharmacologic treatments and references included within selected studies identified from abstract review. Findings Published studies have consistently reported that osteoporosis in older adults is caused by an imbalance of bone resorption in excess of bone formation. The dominant factor leading to bone loss in older adults appears to be gonadal sex steroid deficiency, with multiple genetic and biochemical factors, such as vitamin D deficiency or hyperparathyroidism, that may accelerate bone loss. Conditions that adversely affect growth and development may limit development of peak bone mass and accelerate subsequent bone loss. Studies of bone microarchitecture have shown that trabecular bone loss begins in the third decade of life, before gonadal sex steroid deficiency develops, whereas cortical loss typically begins in the sixth decade, about the time of menopause in women and about the same age in men. Antiresorptive agents for the treatment of osteoporosis act primarily by limiting osteoclast activity, whereas osteoanabolic agents, such as teriparatide, act primarily by stimulating osteoblastic bone formation. Clinical investigation of new compounds for the treatment of osteoporosis is mainly directed to those that stimulate bone formation or differentially decrease bone resorption more than bone formation. Therapies for osteoporosis are associated with adverse effects, but in patients at high risk of fracture, the benefits generally far outweigh the risks. Implications Current osteoporosis therapies mitigate or reverse the loss of bone associated with age-related decreases of gonadal sex steroids, increase bone strength, and reduce fracture risk. With improved knowledge of the pathophysiology of osteoporosis, new targets for therapeutic intervention have been identified. Clinical investigations of potential new treatments for osteoporosis are primarily directed to stimulating osteoblastic bone formation or to modulating the balance of bone resorption and formation in ways that improve bone strength.
AB - Purpose The objectives of this article are to review the pathophysiology of bone loss associated with aging and to review current pharmacologic approaches for the treatment of osteoporosis. Methods A literature search with PubMed was performed with the terms osteoporosis and pathophysiology and osteoporosis and treatment and limited to studies written in English that were published within the preceding 10 years. Given the large number of studies identified, we selectively reviewed those studies that contained primary data related to osteoporosis pathophysiology or osteoporosis pharmacologic treatments and references included within selected studies identified from abstract review. Findings Published studies have consistently reported that osteoporosis in older adults is caused by an imbalance of bone resorption in excess of bone formation. The dominant factor leading to bone loss in older adults appears to be gonadal sex steroid deficiency, with multiple genetic and biochemical factors, such as vitamin D deficiency or hyperparathyroidism, that may accelerate bone loss. Conditions that adversely affect growth and development may limit development of peak bone mass and accelerate subsequent bone loss. Studies of bone microarchitecture have shown that trabecular bone loss begins in the third decade of life, before gonadal sex steroid deficiency develops, whereas cortical loss typically begins in the sixth decade, about the time of menopause in women and about the same age in men. Antiresorptive agents for the treatment of osteoporosis act primarily by limiting osteoclast activity, whereas osteoanabolic agents, such as teriparatide, act primarily by stimulating osteoblastic bone formation. Clinical investigation of new compounds for the treatment of osteoporosis is mainly directed to those that stimulate bone formation or differentially decrease bone resorption more than bone formation. Therapies for osteoporosis are associated with adverse effects, but in patients at high risk of fracture, the benefits generally far outweigh the risks. Implications Current osteoporosis therapies mitigate or reverse the loss of bone associated with age-related decreases of gonadal sex steroids, increase bone strength, and reduce fracture risk. With improved knowledge of the pathophysiology of osteoporosis, new targets for therapeutic intervention have been identified. Clinical investigations of potential new treatments for osteoporosis are primarily directed to stimulating osteoblastic bone formation or to modulating the balance of bone resorption and formation in ways that improve bone strength.
KW - Key words aging
KW - bisphosphonate
KW - bone
KW - bone mineral density
KW - menopause
KW - osteoporosis
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U2 - 10.1016/j.clinthera.2015.06.006
DO - 10.1016/j.clinthera.2015.06.006
M3 - Review article
C2 - 26163201
AN - SCOPUS:84940719700
SN - 0149-2918
VL - 37
SP - 1837
EP - 1850
JO - Clinical therapeutics
JF - Clinical therapeutics
IS - 8
ER -