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Related Concept Videos

Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

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Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
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Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

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In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
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Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

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Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
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Factors Influencing Drug Absorption: Disease States and Pharmacology01:25

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Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
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Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption01:23

Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption

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Understanding the physiological differences in the pediatric population is crucial for effective pharmacotherapy. Neonates, infants, and children exhibit significant variations in gastric pH, gastric emptying time, intestinal transit time, and biliary function. These variations profoundly affect oral drug absorption, necessitating a nuanced approach to pediatric dosing.Neonates present with a unique physiological profile, having a gastric pH greater than 4 and faster and more irregular gastric...
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Factors Affecting Drug Response: Overview01:21

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When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
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Antiresorptives: Safety Concerns-Clinical Perspective.

Jacques P Brown1

  • 11 CHU de Québec Research Centre, Laval University, Québec City, Canada.

Toxicologic Pathology
|October 26, 2017
PubMed
Summary

Antiresorptive drugs like bisphosphonates and denosumab are common osteoporosis treatments. Long-term use may rarely cause osteonecrosis of the jaw and atypical femur fractures.

Area of Science:

  • Pharmacology
  • Orthopedics
  • Bone Metabolism

Background:

  • Antiresorptive drugs, including amino-bisphosphonates and denosumab, have been primary osteoporosis therapies for over two decades.
  • Osteoporosis management often requires lifelong antifracture treatment.
  • Phase III trials excluded many patients, limiting real-world applicability.

Purpose of the Study:

  • To review the long-term safety profile of antiresorptive drugs used in osteoporosis.
  • To discuss rare adverse events associated with prolonged antiresorptive therapy.
  • To explore current hypotheses regarding the pathogenesis of osteonecrosis of the jaw and atypical femur fractures.

Main Methods:

  • Analysis of postmarketing reports and long-term clinical data (>5 years).
Keywords:
atypical femur fracturebisphosphonatesdenosumabosteonecrosis of the jaw

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  • Review of incidence rates for rare adverse events in osteoporosis patients.
  • Synthesis of recent pathogenic hypotheses for osteonecrosis of the jaw and atypical femur fractures.

    • Main Results:

    • Long-term use of antiresorptive drugs is associated with rare adverse events like osteonecrosis of the jaw (ONJ) and atypical femur fractures (AFFs).
    • The incidence of ONJ in osteoporosis patients is slightly elevated compared to the general population (0.001%–0.01%).
    • AFF incidence increases with prolonged bisphosphonate exposure, ranging from 1.8 to 113 per 100,000 person-years.

    Conclusions:

    • While effective, long-term antiresorptive therapy necessitates awareness of rare but serious adverse events.
    • Understanding the incidence and risk factors for ONJ and AFFs is crucial for patient safety.
    • Further research into the pathogenic mechanisms of these rare events is warranted.