Related Experiment Video

Updated: Jun 27, 2026

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
07:03

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro

Published on: June 16, 2022

Large osteoclasts in pediatric osteogenesis imperfecta patients receiving intravenous pamidronate

Moira S Cheung1, Francis H Glorieux, Frank Rauch

  • 1Genetics Unit, Shriners Hospital for Children and McGill University, Montreal, Quebec, Canada.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|December 10, 2008
PubMed

Insights

Pamidronate treatment for pediatric osteogenesis imperfecta (OI) increases osteoclast size and nuclei count. These changes, previously thought to be toxic, are likely part of the drug's therapeutic mechanism.

Area of Science:

  • Pediatric Endocrinology
  • Bone Biology
  • Pharmacology

Background:

  • Intravenous pamidronate is a common treatment for pediatric osteogenesis imperfecta (OI).
  • Previous studies noted osteoclast changes during pamidronate therapy, raising concerns about potential toxicity.
  • The exact implications of these osteoclast alterations remain unclear.

Purpose of the Study:

  • To investigate osteoclast morphology changes in pediatric OI patients before and after pamidronate treatment.
  • To determine if observed osteoclast abnormalities indicate drug toxicity or are related to the therapeutic mechanism.

Main Methods:

  • Analysis of paired iliac bone specimens from 44 pediatric OI patients.
  • Specimens were collected before and after 2-4 years of cyclical intravenous pamidronate therapy.
  • Osteoclast parameters including diameter, nuclearity, and presence of large osteoclasts (LOcs) were quantified.

Main Results:

  • Pamidronate treatment significantly increased average osteoclast diameter (18%) and nuclearity (43%).
  • The prevalence of large osteoclasts (LOcs > 50 µm) rose from 14% to 52% post-treatment.
  • Samples with LOcs showed increased core width and cancellous bone volume, suggesting improved bone accrual, not toxicity.

Conclusions:

  • Observed osteoclast changes, including the emergence of large osteoclasts, during pamidronate therapy for OI are not indicative of toxicity.
  • These morphological alterations are likely integral to the mechanism of action of pamidronate in treating osteogenesis imperfecta.

More Related Videos

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders11:47

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

Published on: June 8, 2014

Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
Bone Disorders01:29

Bone Disorders

Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Skeleton and Calcium Homeostasis01:21

Skeleton and Calcium Homeostasis

Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
Bone Cells and Tissue01:30

Bone Cells and Tissue

Bones contain a relatively small number of cells entrenched in a matrix of organic and inorganic components. Although bone cells compose only a small amount of the bone volume, they are crucial to its function. Four types of cells are found within the bone tissue— osteoblasts, osteocytes, osteogenic cells, and osteoclasts.
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the periosteum and...