Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Part 1 Molecular and cellular environment of bone
- Part II Determinants of peak bone mass
- Part III Pathophysiology of the aging skeleton
- Part IV Clinical aspects of osteoporosis
- 17 Biochemical markers of bone turnover
- 18 Radiologic assessment of osteoporosis
- 19 Bone mineral density measurements
- 20 Hormone replacement therapy
- 21 Selective estrogen receptor modulators
- 22 Bisphosphonate therapy of osteoporosis
- 23 The action of fluoride on bone
- 24 PTH peptides as anabolic agents in bone
- 25 Vitamin D and vitamin D analogs as therapeutic agents
- Index
22 - Bisphosphonate therapy of osteoporosis
Published online by Cambridge University Press: 01 June 2011
- Frontmatter
- Contents
- List of contributors
- Preface
- Part 1 Molecular and cellular environment of bone
- Part II Determinants of peak bone mass
- Part III Pathophysiology of the aging skeleton
- Part IV Clinical aspects of osteoporosis
- 17 Biochemical markers of bone turnover
- 18 Radiologic assessment of osteoporosis
- 19 Bone mineral density measurements
- 20 Hormone replacement therapy
- 21 Selective estrogen receptor modulators
- 22 Bisphosphonate therapy of osteoporosis
- 23 The action of fluoride on bone
- 24 PTH peptides as anabolic agents in bone
- 25 Vitamin D and vitamin D analogs as therapeutic agents
- Index
Summary
Preclinical history
About 100 years ago German chemists discovered that inorganic pyrophosphate could prevent deposition of calcium salts from solution. This observation was the basis of the industrial use of polyphosphates for prevention of calcium carbonate deposition in pipes.
The first biological effect of a pyrophosphate analog was demonstrated in 1968 when Fleisch and his associates in Switzerland found that these agents could inhibit vitamin D-induced aortic calcification in rats (Schibler et al., 1968). Subsequent collaboration of the Swiss investigators with Dr M. D. Francis and his colleagues at Procter and Gamble resulted in the development of bisphosphonates which could be applied to the treatment of a variety of human disorders, the most common of which is osteoporosis.
Chemistry
The bisphosphonates, which were initially termed diphosphonates, are compounds which have two C—P bonds. The compounds are referred to as geminal bisphosphonates if the two bonds are found on the same carbon atom (P—C—P), although this class of compounds is usually simply termed bisphosphonates.
The bisphosphonates are analogs of inorganic pyrophosphate whose core structure has a P—O—P structure. The substitution of an alkyl group confers resistance to hydrolysis to the bisphosphonates whereas inorganic pyrophosphate is highly susceptible to hydrolysis by pyrophosphatases such as alkaline phosphatase.
- Type
- Chapter
- Information
- The Osteoporosis Primer , pp. 304 - 317Publisher: Cambridge University PressPrint publication year: 2000