Tag Archive for: osteoporosis

Laura Tosi, M.D., celebrated as a 2024 POSNA Hall of Fame inductee

Dr. Tosi at the POSNA Hall of Fame induction ceremonyLaura Tosi, M.D., was one of four inductees nominated into the Pediatric Orthopaedic Society of North America (POSNA) Hall of Fame, which honors members who have displayed dedication to teaching and mentoring, studying musculoskeletal conditions in children and caring for children with musculoskeletal conditions.

“I was particularly pleased to be recognized because my contributions have not been typical,” said Dr. Tosi. “I have never developed a new surgical technique or made a scientific breakthrough. Rather, I have come to recognize the importance of maintaining good bone health to support the quality of life of our patient population.”

Dr. Tosi began her career at Children’s National Hospital in 1984, focused on the care of children with disabilities such as spina bifida, cerebral palsy and arthrogryposis. Over the course of her tenure, she noted that children with these conditions were surviving at increasingly higher rates, but their quality of life was often derailed by disuse osteoporosis and pathologic fractures.

Her work on secondary fragility fracture prevention ultimately led her to develop the Children’s National Bone Health Program, which launched in 2003. She has since leveraged this program to expand interest in rare bone disease, thanks in part, to her collaborative work with the National Institutes of Health and Osteogenesis Imperfecta Foundation.

“We are all so proud of Dr. Tosi for this amazing recognition,” said Matthew Oetgen, M.D., M.B.A., chief of orthopaedic surgery and sports medicine at Children’s National. The POSNA Hall of Fame is a BIG DEAL! There really is no more powerful recognition than that of colleagues, and this award shows how much of an impact Dr. Tosi has had worldwide. She is a true leader in pediatric orthopaedic surgery and pediatric bone health, and this award is well deserved. Her dedication to Children’s National, the children of the region and us, her partners, has been unwavering, and we thank her for it.”

How a rare disease treatment could impact millions

Post-mortem image shows significant narrowing of the artery in an infant with GACI due to buildup of calcium crystals between the vessel wall’s inner and middle layers. Inset: Normal non-calcified artery. Patients with GACI lack the protein ENPP1, which is responsible for creating pyrophosphate. Pyrophosphate plays a critical role in preventing calcium crystallization and accumulation.

Post-mortem image shows significant narrowing of the artery in an infant with GACI due to buildup of calcium crystals between the vessel wall’s inner and middle layers. Inset: Normal non-calcified artery. Patients with GACI lack the protein ENPP1, which is responsible for creating pyrophosphate. Pyrophosphate plays a critical role in preventing calcium crystallization and accumulation.

One of the first patients I ever saw with generalized arterial calcification of infancy (GACI) was actually the third child with this condition born to the same parents. GACI is a rare genetic disease, occurring in 1 of 200,000 live births. Unfortunately, as is common in GACI, two of the family’s children previously succumbed to the disorder within the first 6 weeks of life.

GACI causes calcium to build up in the arteries, causing critical blockages that reduce blood flow to organs leading to diminished function, including stroke, heart attack, and death.

Etidronate, a pyrophosphate analog developed to treat osteoporosis, has shown limited success at replacing the pyrophosphate for patients with GACI. However, more than 55 percent of children with GACI still die before their first birthday.

We need more effective solutions. Several treatment options are in development, including the administration of ENPP1 bound to an antibody, which has shown to provide a marked survival improvement in a mouse model of the disease.

These new solutions could translate to more effective treatment of GACI but also other conditions causing calcification in the arteries, particularly the calcium buildup associated with long-term kidney disease. A treatment that potentially reduces morbidity for the estimated 20 million plus Americans with chronic kidney disease would have tremendous health and economic benefits.

Developing more targeted therapies for GACI could allow this to be the outcome for many more patients, both children with GACI and potentially also patients affected by chronic kidney disease.

About the Author

Carlos Ferreira LopezCarlos Ferreira Lopez, M.D.
Geneticist Specialist