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Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management.

Dalle Carbonare L, Zanatta M, Gasparetto A, Valenti MT - Drug Healthc Patient Saf (2010)

Bottom Line: These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action.Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation.The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.

View Article: PubMed Central - PubMed

Affiliation: Clinic of Internal Medicine D, Department of Medicine, University of Verona, Italy.

ABSTRACT
Bisphosphonates (BPs) are widely used in the treatment of postmenopausal osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively). The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis), and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.

No MeSH data available.


Related in: MedlinePlus

Molecular structure of pyrophosphate and of the most common nitrogen-containing bisphosphonates.
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f1-dhps-2-121: Molecular structure of pyrophosphate and of the most common nitrogen-containing bisphosphonates.

Mentions: BPs are analogs of inorganic pyrophosphate, and composed of an enzyme-resistant phosphorus-carbon-phosphorus (P-C-P) structure able to adhere strongly to hydroxyapatite crystals (Figure 1). They have a relatively simple core structure, and the pharmacologic properties of each BP molecule depend on lateral chains, named R1 and R2.8 The P-C-P nucleus and R1 lateral chain are responsible for anchoring the drug to the bone mineral matrix, while R2 has biologic and therapeutic actions. The presence of a hydroxyl group in R1 markedly increases BP affinity for the bone matrix, while the nitrogen atom in R2 is responsible for antiresorptive potency.5


Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management.

Dalle Carbonare L, Zanatta M, Gasparetto A, Valenti MT - Drug Healthc Patient Saf (2010)

Molecular structure of pyrophosphate and of the most common nitrogen-containing bisphosphonates.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108695&req=5

f1-dhps-2-121: Molecular structure of pyrophosphate and of the most common nitrogen-containing bisphosphonates.
Mentions: BPs are analogs of inorganic pyrophosphate, and composed of an enzyme-resistant phosphorus-carbon-phosphorus (P-C-P) structure able to adhere strongly to hydroxyapatite crystals (Figure 1). They have a relatively simple core structure, and the pharmacologic properties of each BP molecule depend on lateral chains, named R1 and R2.8 The P-C-P nucleus and R1 lateral chain are responsible for anchoring the drug to the bone mineral matrix, while R2 has biologic and therapeutic actions. The presence of a hydroxyl group in R1 markedly increases BP affinity for the bone matrix, while the nitrogen atom in R2 is responsible for antiresorptive potency.5

Bottom Line: These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action.Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation.The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.

View Article: PubMed Central - PubMed

Affiliation: Clinic of Internal Medicine D, Department of Medicine, University of Verona, Italy.

ABSTRACT
Bisphosphonates (BPs) are widely used in the treatment of postmenopausal osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively). The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis), and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.

No MeSH data available.


Related in: MedlinePlus