Optimising antiresorptive therapies in postmenopausal women : Why do we need to give due consideration to the degree of suppression?

Accelerated bone turnover with bone resorption exceeding bone formation is a major mechanism underlying postmenopausal bone loss and hence the development of osteoporosis. Accordingly, inhibition of bone resorption is a rational approach for the prevention of osteoporosis. In this context, the most...

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Bibliographic Details
Published in:Drugs (New York, N.Y.) N.Y.), 2006-01, Vol.66 (15), p.1909-1918
Main Authors: KARSDAL, Morten A, QVIST, Per, CHRISTIANSEN, Claus, TANKO, Laszlo B
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Biological and medical sciences
Bone Density - drug effects
Bone Density Conservation Agents - therapeutic use
Bone Resorption - complications
Bone Resorption - drug therapy
Bones, joints and connective tissue. Antiinflammatory agents
Diphosphonates - therapeutic use
Diseases of the osteoarticular system
Female
Fractures, Bone - etiology
Humans
Malformations and congenital and or hereditary diseases involving bones. Joint deformations
Medical sciences
Osteoporosis, Postmenopausal - complications
Osteoporosis, Postmenopausal - drug therapy
Osteoporosis. Osteomalacia. Paget disease
Pharmacology. Drug treatments
Postmenopause
RANK Ligand - immunology
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Summary:Accelerated bone turnover with bone resorption exceeding bone formation is a major mechanism underlying postmenopausal bone loss and hence the development of osteoporosis. Accordingly, inhibition of bone resorption is a rational approach for the prevention of osteoporosis. In this context, the most logical option, hormone replacement therapy, reverses the rate of bone turnover to premenopausal levels, whereas the magnitude of inhibition by amino-bisphosphonates and the recently introduced anti-receptor activator of NFkappaB ligand (RANKL) antibody often exceeds this. As bone turnover has crucial implications for the continuous renewal of bone tissue, the over-suppression of bone turnover has potential consequences for bone quality and strength. Long-term treatment with potent bisphosphonates has recently been associated with osteonecrosis of the jaw and dose-dependent increases in micro-crack accumulation in animals. Although these observations are the subject of ongoing discussions, it is timely to discuss whether the over-suppression of bone turnover below premenopausal levels is really our ultimate goal when defining the success criteria for antiresorptive agents. In this review, the implications of high and excessively low bone turnover of endogenous origin for bone quality, fracture risk and integrity of the jaw are discussed. In addition, animal and clinical research revealing initial findings regarding the potential adverse effects of drug-induced suppression of bone remodeling are summarised. The inhibition of bone resorption, which is either transient between doses (e.g. with calcitonin) or does not exceed premenopausal levels (with hormone replacement therapy or selective estrogen receptor modulators), is preferable because it not only provides similar antifracture efficacy but can also assist in the maintenance of the dynamic repair of micro-cracks/micro-fractures.
ISSN:0012-6667
1179-1950
DOI:10.2165/00003495-200666150-00002