Osteoporosis, a type of bone disease, is an often overlooked consequence of aging, but make no mistake, it is serious. A woman’s risk of breaking a hip due to osteoporosis is equal to her risk of breast, ovarian, and uterine cancer combined. Similarly, a man over 50 is more likely to break a bone due to osteoporosis than he is to get prostate cancer. Following a series of animal studies, a group of researchers from the Netherlands and Germany discovered a new target that may be critical for the treatment of osteoporosis; they identified human plastin 3 (PLS3) gene mutations as a possible cause of the disease.

"Osteoporosis poses an urgent health problem that is going to become more important as years go [by] with the numbers of elderly people in the community continuing to increase," said Professor Brunhilde Wirth, head of the Institute of Human Genetics, University of Cologne, Germany. "Although in itself it is not a fatal illness, large numbers of people die prematurely as a result of health complications following falls.” Wirth is presenting her findings Saturday at the annual conference of the European Society of Human Genetics.

Risk Factors for Osteoporosis

Bones may appear to be hard and static, but actually, they are living, growing tissue. Osteoporosis, which is caused by losing too much bone, making too little bone, or both, is a disease that causes bones to become weak and easily broken. Risk factors for osteoporosis include being over 50, being female, menopause, low body weight (being small and thin), and family history. There are controllable risk factors, as well, including not getting enough calcium and vitamin D; not eating enough fruits and vegetables; eating too much protein, sodium, and caffeine; inactivity; smoking; and drinking too much. Because of its prevalence — the disease affects about a quarter of all post-menopausal women — osteoporosis has become a major health problem in many aging societies.

Wirth and her colleagues began their study of possible causes by examining the development of zebrafish embryos in which PLS3 was knocked out during the three- and five-day-old stage. The team discovered that the zebrafish had massive impairment of craniofacial skeletal development. Yet, when the team added human PLS3, the zebrafish became fully restored. Adding two proteins — actinin 1 and actinin 4, both involved in building the scaffolding for cells — a similar restoration process occurred.

“It seems that these proteins can compensate for the loss of PLS3,” Wirth said in a press release. “Thus we have been able to verify the essential role of actin in bone development and maintenance."  In subsequent mouse studies, Wirth and her co-researchers confirmed their findings.

All of this came as a surprise to her, since mutations in the PLS3 gene had not previously been known to be related to osteoporosis and fractures, or to play a role in bone formation.

"Since we know that about five percent of the human population expresses higher than normal levels of PLS3, we can hypothesize that these people may be protected against osteoporosis," Wirth said. “We believe that our work has led to a better understanding of the condition and has pointed the way towards improved diagnosis and prevention, and, we hope, an effective treatment in the future.”