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The osteoporosis-pseudoglioma syndrome (OPPG) is an autosomal recessive disorder that affects skeletal strength and vision.

The first sign of OPPG is often congenital or infancy-onset vision loss due to abnormal blood vessel development in the eye. However, some people affected with OPPG have skeletal fractures as their earliest findings. These fractures occur in the context of very low bone mass, a trait that can be measured radiologically.

We first reported mutations in the gene LRP5 as the cause of OPPG. LRP5 (Low density lipoprotein receptor-related protein 5) is a cell surface receptor, which we think is important for improving the function of bone-forming cells (osteoblasts). Persons completely lacking LRP5 have OPPG. We and other investigators have also noted that individuals who carry 1 non-working LRP5 gene (LRP5 carriers) are at increased risk for having moderately low bone mass, putting them at significantly increased risk for developing common osteoporosis. Carriers of LRP5 mutations have also been found to be at increased risk for developing an eye disease called exudative vitreoretinopathy.

We have established an international consortium of patients, clinicians and basic scientists to study OPPG and the role of LRP5 in regulating bone strength. Our collaborators are studying the role of LRP5 in the eye. The goals of our consortium are to improve the diagnosis and treatment for persons affected with OPPG, and to extend what we learn from patients and families affected by OPPG to improve the skeletal health of other people.

Pooling resources and sharing ideas is important for advancing our knowledge about OPPG, since we estimate that only 7000 persons in the entire world are affected with this rare disease. Even though OPPG is rare, we predict that there are 14 million LRP5 mutation carriers in the world, all of whom are at increased risk for developing common osteoporosis.

Among the questions we want to answer are:

  1. Can we improve our ability to identify disease-causing mutations in LRP5 among persons with OPPG or in persons with common forms of osteoporosis?

  2. Can we identify medicines and other therapies that will increase bone strength in patients with OPPG by bypassing the need for LRP5? For example, we have found that the drug lithium can increase bone mass in mice that are lacking LRP5. We would like to test (see below) whether lithium therapy will be equally effective, and importantly safe, in human patients with OPPG.

  3. Precisely how does LRP5 influence the function of a cell? For example, does it cause more cells to become bone-forming cells or does it cause bone-forming cells to work better at making bone.

Interested in participating?

We welcome individuals and families who are affected by OPPG to participate in our research by contacting us.

To improve our ability to diagnose OPPG, we are seeking blood samples from patients with OPPG and their unaffected relatives.

To better understand how LRP5 functions within the body, we are seeking bone specimens that may be recovered at the time of a diagnostic or medically-indicated procedure.

We are planning to begin a prospective, open-label study to determine whether oral lithium therapy can improve bone mass in patients with OPPG and their carrier relatives who may have osteoporosis. Because we do not yet know the safety and efficacy of oral lithium therapy in persons with OPPG, we think it will be very important to perform this study in a research setting. Please contact us if you would be interested in being part of this study.

Studying the consequences of OPPG at the cellular, biophysical, and protein levels may help in furthering the development of new therapeutic strategies.

Physicians seeking assistance in making a diagnosis of OPPG are also welcome to contact us.