What is the mechanism of action of this treatment?

The most common treatments for Fibrous Dysplasia (FD) focus on inhibiting osteoclast activity to reduce bone resorption and improve bone strength. Denosumab, a RANKL inhibitor, is a key treatment that works by blocking the RANKL pathway, thereby reducing the formation and activity of osteoclasts, which are cells responsible for bone resorption. This mechanism is crucial for FD patients as it helps to prevent the weakening of bones, reduce the risk of fractures, and manage bone lesions that are characteristic of the disease. By stabilizing bone structure, Denosumab and similar treatments can significantly improve the quality of life for individuals with FD.

What side effects are associated with this type of intervention?

Denosumab, used to treat Fibrous Dysplasia by inhibiting RANK ligand and reducing osteoclast activity, has several known side effects. These include hypocalcemia, increased risk of infections, and potential rebound vertebral fractures if the treatment is discontinued. Another significant risk is osteonecrosis of the jaw. These side effects should be carefully considered and monitored during treatment.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Fibrous Dysplasia. However, Denosumab, which is being studied for this condition, works by inhibiting RANKL to reduce osteoclast activity and bone resorption. This mechanism is similar to other osteoclast inhibitors like bisphosphonates, which are used to treat conditions involving excessive bone resorption, such as osteoporosis and bone metastases. These treatments aim to strengthen bone and reduce the risk of fractures.

What other types of research exist?

Promising novel alternatives to Denosumab for Fibrous Dysplasia patients include bisphosphonates like zoledronic acid and investigational agents such as romosozumab. These treatments target bone resorption and osteoclast activity, potentially offering effective management of FD.

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Monoclonal Antibodies

Denosumab for Fibrous Dysplasia

Phase 2

Recruiting

Led By Alison M Boyce, M.D.

Research Sponsored by National Institute of Dental and Craniofacial Research (NIDCR)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 4 to 14 years

Confirmed diagnosis of fibrous dysplasia

Must not have

Orthopedic procedure performed less than 6-weeks prior to first day of the denosumab administration (Day 0)

Prior history, or current evidence, of osteomyelitis/osteonecrosis of the jaw

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 76 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial tests an injectable medication in children with fibrous dysplasia. The drug works by preventing excessive bone breakdown, aiming to stop the growth of bone lesions. It has shown promise in treating fibrous dysplasia.

Who is the study for?

Children aged 4-14 with Fibrous Dysplasia enrolled in a specific NIH study, weighing at least 12 kg. They must have a guardian who can consent to the trial and agree to use effective contraception if of reproductive age. Exclusions include low calcium levels, untreated hypophosphatemia, recent investigational drug use, safety concerns as per investigator's discretion, pregnancy or lactation, allergy to denosumab, jaw bone issues or recent surgeries.

What is being tested?

The trial is testing denosumab injections every four weeks for one year in children with FD. The goal is to see if it stops the growth of weak and potentially harmful bone lesions. Participants will undergo various tests including dental exams and scans during their hospital stays and local lab visits.

What are the potential side effects?

Denosumab may cause potential side effects such as low calcium levels in blood (hypocalcemia), skin reactions at the injection site, infections due to weakened immune system response, possible impact on growth plates in bones for children.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 4 and 14 years old.

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I have been diagnosed with fibrous dysplasia.

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My guardian or I can understand and are willing to sign the consent form.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had any bone surgery in the 6 weeks before starting denosumab.

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I have had, or currently have, a bone infection or bone death in my jaw.

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I have a dental or oral surgery wound that hasn't healed.

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I plan to undergo a dental surgery during the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 76 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~76 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 76 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Skeletal Burden Score

Secondary study objectives

Adverse events

Change in 18F-NaF PET/CT sentinel lesion intensity (SUVmax)

Change in 18F-NaF PET/CT total lesion activity from baseline to 48 weeks

+3 more

Side effects data

From 2020 Phase 4 trial • 76 Patients • NCT02176382

wrist fracture

breast cancer

throat cancer

vertebral fracture

clavicle fracture

fibula avulsion fracture

humeral fracture

kidney cancer

pancreatitis

rib fracture

shoulder dislocation

100%

80%

60%

40%

20%

Study treatment Arm

Standard Dose Teriparatide

High Dose Teriparatide

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: treatmentExperimental Treatment1 Intervention

treatment arm

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

denosumab

2014

Completed Phase 4

~522440

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Fibrous Dysplasia (FD) focus on inhibiting osteoclast activity to reduce bone resorption and improve bone strength. Denosumab, a RANKL inhibitor, is a key treatment that works by blocking the RANKL pathway, thereby reducing the formation and activity of osteoclasts, which are cells responsible for bone resorption. This mechanism is crucial for FD patients as it helps to prevent the weakening of bones, reduce the risk of fractures, and manage bone lesions that are characteristic of the disease. By stabilizing bone structure, Denosumab and similar treatments can significantly improve the quality of life for individuals with FD.

An anti-RANKL treatment reduces muscle inflammation and dysfunction and strengthens bone in dystrophic mice.RANKL Inhibition in Fibrous Dysplasia of Bone: A Preclinical Study in a Mouse Model of the Human Disease.