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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

Farnesyl pyrophosphate synthase enzyme inhibition potency (IC50) of nitrogen-containing bisphosphonates (inhibition of 50% of maximum enzyme activity). Note that zoledronic acid shows the higher affinity for the mineral matrix combined with the higher inhibition potency of farnesyl pyrophosphate synthase.26Abbreviations: ALN, alendronate; IBN, ibandronate; RIS, risendronate; ZOL, zolendronic acid.
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f2-dhps-2-121: Farnesyl pyrophosphate synthase enzyme inhibition potency (IC50) of nitrogen-containing bisphosphonates (inhibition of 50% of maximum enzyme activity). Note that zoledronic acid shows the higher affinity for the mineral matrix combined with the higher inhibition potency of farnesyl pyrophosphate synthase.26Abbreviations: ALN, alendronate; IBN, ibandronate; RIS, risendronate; ZOL, zolendronic acid.

Mentions: The potency of zoledronic acid appears to be related also to its unique chemical structure. All BPs have a P-C-P nucleus that acts as a bone hook, while R2 is the structure primarily responsible for antiresorptive potency and duration of action. R2 in zoledronic acid is composed of a heterocyclic ring containing two nitrogen atoms (Figure 1).29,30 Biochemical assays have demonstrated the antiresorptive potency of this bisphosphonate. In in vitro analysis of FPP synthase inhibition, zoledronic acid was the most potent BP evaluated, followed by risedronate, ibandronate, alendronate, and pamidronate31 (Figure 2). The ability to inhibit FPP is directly correlated with effectiveness in suppressing bone turnover in vivo.


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)

Farnesyl pyrophosphate synthase enzyme inhibition potency (IC50) of nitrogen-containing bisphosphonates (inhibition of 50% of maximum enzyme activity). Note that zoledronic acid shows the higher affinity for the mineral matrix combined with the higher inhibition potency of farnesyl pyrophosphate synthase.26Abbreviations: ALN, alendronate; IBN, ibandronate; RIS, risendronate; ZOL, zolendronic acid.
© Copyright Policy
Related In: Results  -  Collection

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

f2-dhps-2-121: Farnesyl pyrophosphate synthase enzyme inhibition potency (IC50) of nitrogen-containing bisphosphonates (inhibition of 50% of maximum enzyme activity). Note that zoledronic acid shows the higher affinity for the mineral matrix combined with the higher inhibition potency of farnesyl pyrophosphate synthase.26Abbreviations: ALN, alendronate; IBN, ibandronate; RIS, risendronate; ZOL, zolendronic acid.
Mentions: The potency of zoledronic acid appears to be related also to its unique chemical structure. All BPs have a P-C-P nucleus that acts as a bone hook, while R2 is the structure primarily responsible for antiresorptive potency and duration of action. R2 in zoledronic acid is composed of a heterocyclic ring containing two nitrogen atoms (Figure 1).29,30 Biochemical assays have demonstrated the antiresorptive potency of this bisphosphonate. In in vitro analysis of FPP synthase inhibition, zoledronic acid was the most potent BP evaluated, followed by risedronate, ibandronate, alendronate, and pamidronate31 (Figure 2). The ability to inhibit FPP is directly correlated with effectiveness in suppressing bone turnover in vivo.

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