09/18/2025
It has been a while since I've given an update about our studies. We've had some very exciting things going on in our lab, and I’ve been able to share some of our data from the natural history study, but not been able to share some of the more basic work in mice that has been done in our lab, until now.
Osteopetrosis is sometimes called “marble bone disease” because the bone is very dense and hard, but cracks easily (think what happens when you drop a piece of marble on the floor). As you are aware, osteopetrosis results when the osteoclast, a cell that digs tunnels in bone, is inactive and fails to resorb bone. This results in very dense bone that is brittle.
The Natural History Study
We have been performing a natural history study for the past several years. We presented our findings at the American Society of Bone and Mineral Research (ASBMR) meeting last year and have published these findings in the ASBMR’s journal, the Journal of Bone and Mineral Research (https://pubmed.ncbi.nlm.nih.gov/40913471/). Our data is obtained by studying patients with autosomal dominant osteopetrosis (ADO), many of whom are members of this group. In brief, the data show that ADO patients with the lowest osteoclast function and the highest bone density fracture more than ADO patients with better osteoclast function and lower bone density. Our study also found that ADO patients with the lowest bone turnover markers (another indication that osteoclasts aren’t working properly) have the most fractures. Importantly, we hope to use these measures as “surrogate” endpoints in clinical trials that are designed to test if a potential therapy could be used to treat ADO. Those therapies that increase osteoclast activity and, thereby, lower bone density, could be used to treat ADO, which brings me to findings in our mice.
A New Study in a Mouse Model of ADO Reported at this Year’s ASBMR Meeting
Many years ago, we made a mouse model of ADO and have tested a variety of possible therapies in this mouse model. At this year’s ASBMR meeting Dr. Imran Alam, from our group at Indiana University, reported positive findings in our animal model of ADO. We treated our ADO mice with a drug called vantictumab, which had failed in clinical studies aimed at a different purpose. Patients in those studies, none of whom had osteopetrosis, were given the drug, and had marked increases in bone resorption caused by marked increases in osteoclast activity. Since these patients didn’t have osteopetrosis, they developed very low bone density from overly active osteoclasts and developed osteoporosis, which also leads to fracture (both too high and too low bone density is bad for bone). Working with AshiBio, a biotech company, we tested vantictumab in our mice, who like ADO patients have underactive osteoclasts. In our first study we gave the mice doses of vantictumab that were similar to what the patients in the previous studies received, and in 3 months their bone density went below that of normal mice not given drug. Even though the bone density decreased below normal, we knew that this was a big success because we could give less drug. In the second study we used lower doses for one month and the bone density became normal. A quick word of caution: As excited about these results as we are, we realize that mice are not people, and just because something works in a mouse model doesn’t mean we can go right into people. In short, there is a lot of work that needs to be done. However, since vantictumab has been safely given to patients (with the exception of patients losing bone, which is the “side effect” that we were looking for) it is possible that we could start a clinical trial to see if vantictumab is useful as a therapy in people who have osteopetrosis in the not too distant future.
Michael J. Econs, MD
Glenn W. Irwin, Jr. Professor of Endocrinology and Metabolism
Director, Division of Endocrinology and Metabolism
Distinguished Professor of Medicine and Medical and Molecular Genetics
