Boning Up on Loeys-Dietz Syndrome

Johns Hopkins cardiologist Hal Dietz

Earlier diagnosis and better management of vascular and cardiac complications have led to dramatic improvements in the lives of patients with the connective tissue disorder Loeys-Dietz syndrome (LDS). But a recent Johns Hopkins study, believed to be the largest examination of skeletal fragility in LDS patients, shows that people with the condition are also prone to bone fractures and low bone mineral density.

In a survey and chart review of 57 LDS patients, researchers found that 33 patients (58 percent) had at least one fracture, and 14 (25 percent) had two or more. Participants reported a total of 51 fractures—35 in the upper extremity, 14 in the lower extremity and two in the spine; the forearm and wrist were most commonly injured. Most fractures resulted from falls.

Investigators calculated that LDS patients had a 50 percent risk of fracture by age 14 and greater overall incidence of fractures compared with the general population. In a subset who had dual-energy X-ray absorptiometry scans available for review, at least 60 percent had low or very low bone mineral density in the spine, hip and/or femoral neck.

First described by Johns Hopkins cardiologist Hal Dietz and colleagues in 2005, LDS is characterized by vascular aneurysms and blood vessel tortuosity, hypertelorism and bifid uvula or cleft palate. Patients with LDS are at high risk for progressive arterial aneurysms commonly leading to aortic dissection and rupture. Early recognition of the condition, combined with advances in medical and surgical management of its vascular complications, can improve life expectancy, the authors say.

“In light of our findings about patients’ increased risk for osteopenia and osteoporosis,” Dietz says, “physicians should counsel their patients about their predisposition to low bone mineral density and higher fracture risk. We are hopeful that this issue will prove amenable to medical therapies, diet and exercise.”

Adds orthopedic surgeon and senior study author Paul Sponseller, “Further studies focusing on bone structure and function, as well as on the molecular mechanisms that drive increased fracture risk and osteopenia, will pave the way to developing targeted therapies.”