Bisphosphonates
A new era in the treatment of disorders of bone began about 30 years ago with the introduction of bisphosphonates into clinical practice. Bisphosphonates are deposited on the surface of the bones, inhibit osteoclasts and thus resorption of bone. Consequen
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Bisphosphonates
Biochemical markers of bone remodelling
Formation
A new era in the treatment of disorders of bone began about 30 years ago with the introduction of bisphosphonates into clinical practice. Bisphosphonates are deposited on the surface of the bones, inhibit osteoclasts and thus resorption of bone. Consequently, these drugs have long been given to patients with Morbus Paget, hypercalcaemia, multiple myeloma and osseous metastases. Bisphosphonates not only inhibit resorption of bone, they also inhibit growth of metastases in the bone and bone marrow. Bisphosphonates inhibit resorption in osteoporosis and – in particular the latest aminobisphosphonates – have no adverse effects on bone formation and therefore lead to a long-lasting (periods of years) positive bone balance. Bisphosphonates have been successfully used for the prevention and therapy in all forms of osteoporosis. Compact and spongy bone show equal increases in bone density (Fig. 15.1). Moreover, the long-term incorporation of bisphosphonates into the bones has no detectable deleterious inÀuence on bone quality and strength. The concept of “frozen bone” under bisphosphonate therapy is simply not true. A basic level of remodelling is consistently maintained even under long-term bisphosphonate therapy. Disturbances of mineralization have not been observed with the new bisphosphonates currently in use.
Resorption
Onset of therapy
Time
Bone density
Onset of therapy
Time
Fig. 15.1. Bone remodelling and bone density under antiresorptive therapy with bisphosphonates
The nitrogen-containing bisphosphonates are today the most effective medications available for the
R. Bartl, B. Frisch, Osteoporosis, DOI 10.1007/978-3-540-79527-8_15, © Springer-Verlag Berlin Heidelberg 2009
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15 Bisphosphonates
treatment of all forms of osteoporosis in both men and women, young and old, congenital and acquired osteoporosis, primary and secondary, high and low turnover, and in pre-, peri- and post-menopausal and involutional osteoporoses. Bisphosphonates have also been given to children – even very young ones – but this should only be done in authorized paediatric centres under strictly controlled indications and conditions.
15.1 A Brief Survey of Bisphosphonates These are synthetic compounds, analogues of pyrophosphate in which the oxygen atom of the central P–O–P bond has been replaced by carbon, resulting in a P–C–P group. This exchange has made the bisphosphonates resistant to enzymatic hydrolysis. In addition, different bisphosphonates can be synthesized by substitution of both hydrogen atoms on the carbon atom, and these bisphosphonates differ in their biological properties, activities, pharmacodynamics and toxicity. There are two side chains (Fig. 15.2): Ɣ One binds to bone mineral Ɣ One determines class and potency (nitrogen molecule) The dynamics of these new bisphosphonates manifest themselves in their potency – they are 20,000 times more potent than etidronate, the ¿rst generation bisphosphonate (Table 15.1). Bisphosphonates have a
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