ARRA IMPACT REPORT:
Public Health Burden
is a disease in which the bones become weak and are more likely to break. In
the United States, more than 40 million people either already have osteoporosis,
or are at high risk due to low bone mass. Osteoporosis can occur in both men
and women and at any age, but it is most common in older women. People with
osteoporosis most often break bones in the hip, spine, and wrist.
Bone Structure and Fracture Risk
After NIH-funded researchers demonstrated that low bone mineral
density (BMD) predicts a person’s risk of fracture and showed that people can
take steps to protect their bones, clinicians began measuring BMD to identify
people who have fragile bones. BMD, however, does not explain or predict all
osteoporotic fractures. Through ARRA, researchers examined other aspects
of bone quality by:
- Comparing the bone structure of people with and without type 2 diabetes, and those in both groups who have and do not have fragility fractures.1
Researchers observed that the bones of women who have type 2 diabetes were more porous (an indicator of decreased bone strength) than those of women without the disease. Furthermore, the investigators found a trend toward higher bone marrow fat in the women with diabetes, in particular, in those whose diabetes was not well controlled. The scientists plan to expand their studies and further explore whether bone porosity relates to fracture risk in these patients.
- Developing a research team that used advanced imaging techniques to generate a model of the porous portion of the thigh bone.2
The data generated through this work will provide a reference standard for efforts to identify regions of bone that are most at risk for fracture.
Genetics of Osteoporosis
Identification of genetic variants associated with fracture risk. Although genetic differences account for up to 75 percent of bone mineral density, the exact genes involved remain a mystery. NIH ARRA-funded activities related to the genetics of osteoporosis include mapping genetic variation at several million sites in the genomes of 3600 women and 5200 men, whose detailed clinical data related to osteoporotic fracture risk are already available.3 Analyses to identify genetic variants associated with fracture risk are underway. The data will be made available for sharing with other researchers through the NIH data repository of genotype and phenotype (dbGaP), enabling a wide range of studies relevant to osteoporosis and other diseases.
Molecular Mechanisms of Osteoporosis
Identification of molecular mechanisms of bone build-up and breakdown could provide new targets for osteoporosis drugs. NIH ARRA-funded research studied the molecular mechanisms of osteoporosis by showing that a set of genes normally involved in controlling how a cell degrades its own components, are also important in regulating the bone breakdown process.4 The researchers developed a mouse model that lacks these genes and showed that the animals are resistant to the type of osteoporosis that sometimes accompanies menopause.
Bone Development and Maturation
Osteoporosis is often called a “pediatric disease with geriatric consequences.” Bone formed in childhood and adolescence is an important determinant of lifelong skeletal health. Through ARRA, investigators are identifying strategies that can give our nation’s children long-term skeletal benefits. ARRA-funded projects include:
- Assessing the effect of caloric intake on skeletal health during rapid growth. The results show that caloric restriction in young growing animals leads to smaller mice with weaker bones.5 Although the studies were conducted in mice, evidence that chronic under-nutrition during growth decreases peak bone mass in adulthood suggests that diet could influence children’s future risk of developing osteoporosis as adults.
- Updating a commonly used method of assessing skeletal maturity to reflect differences among races, and making the data available to researchers over the Internet.6 The current method uses data from Caucasian children. A more accurate method of determining skeletal growth in African American, Asian American, or Hispanic children will allow them to receive better clinical care.
Bone Strengthening through Exercise
Exploring how bone cells adapt to mechanical stress. Like muscle, bone is living tissue that responds to exercise by becoming stronger. ARRA-funded scientists built on this knowledge by exploring how bone cells adapt to mechanical stresses.7,8,9 Unraveling the molecular pathways that control bone’s response to exercise and normal daily activities may facilitate the development of drugs that preserve bone in people who have limited mobility.
Contributing NIH Institutes & Centers
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)