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ARRA Investments in Osteoporosis and Fracture Healing


Public Health Burden
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which increases a person’s risk of fractures of the hip, spine, and wrist.  One out of every two women and one in four men over 50 will have an osteoporosis-related fracture in their lifetime.  10 million Americans already have osteoporosis, and 34 million more are at risk because they have low bone mass.

Bone Structure and Fracture Risk
Osteoporosis is a “silent” disease, as it does not produce any symptoms until bones start to break.  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 are examining other aspects of bone quality by:
  • Comparing bone structure of people with and without type 2 diabetes1, and those in both groups who have and do not have osteoporotic fractures.  Standard measures of BMD do not accurately predict fractures in people who have type 2 diabetes, as these patients tend to have fragile bones and, paradoxically, a higher-than-normal BMD.  Identification of a measurable indicator of bone health in diabetics could guide development of new drugs to prevent fractures.  The information also could be integrated into fracture-prediction models for the general population.
  • Exploring how fat in the bone marrow cavity affects skeletal health2. Recent studies of bone and fat cells show that both come from a common precursor cell.  As a next step, researchers are examining whether bone marrow fat concentrations in people are associated with their BMD, and how rapidly their bones breakdown and re-form.  In addition to possibly providing another measurable parameter that clinicians could consider when calculating fracture risk, knowledge of the relationship between bone and fat could reveal new therapeutic targets.
Genetics of Osteoporosis
The sex and racial differences in peak bone mass and osteoporosis risk are well-documented.  Although genetic differences account for up to 75 percent of bone mineral density, the exact genes involved remain a mystery.  With ARRA funds, researchers are:
  • Developing a resource that investigators can use to identify genetic changes that influence bone health3.  The discovery of genetic variants that protect against osteoporosis or increase a person’s risk of having low bone mass is likely to suggest targets for the development of drugs that prevent fragility fractures.  Moreover, investigators could use genetic markers to identify appropriate participants for clinical trials.
  • Searching for a genetic explanation for the disparities in peak bone mass between men and women4.  Identification of genes responsible for the intrinsic sex differences in bone build-up and breakdown could provide new targets for osteoporosis drugs, and may complement findings from other ARRA-supported research into the mechanisms by which estrogen preserves bone5.
Bone Strengthening through Exercise
Like muscle, bone is living tissue that responds to exercise by becoming stronger.  ARRA-funded scientists are building on this knowledge by:
  • Exploring how bone cells adapt to mechanical stresses6,7,8. 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.

  • Comparing the ability of two exercise regimens to improve bone health in older men who have low bone mass9. Exercise-based interventions are attractive alternatives to medication because they cost less, have few side effects, and confer additional health benefits.
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.  Projects include:
  • Assessing the extent to which a mother’s caloric intake and fat consumption influence fetal bone formation and, ultimately, the strength of her offspring’s mature bones10.  Although the studies are being conducted in mice, evidence that maternal diet influences peak bone mass in adulthood would suggest that a pregnant woman’s diet is a modifiable risk factor that could influence her children’s risk of developing osteoporosis as adults.
  • Investigating the extent to which the bone-building effects of childhood activity translate into skeletal health during adulthood11.
  • Updating a commonly used method of assessing skeletal maturity to reflect differences among races, and making the data available to researchers over the Internet.  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 care12.
Fracture Repair
Although new classes of drugs are significantly reducing the risk of fragility fractures, researchers are continuing to explore strategies to promote bone healing when bones break because of osteoporosis.  Examples of ARRA-funded activities include:
  • Testing materials that may be more durable than the cements that are used to stabilize fragile bones13. Older people who break a hip, for example, may need an artificial joint or other implant which surgeons attach to the bone with a cement-like substance that destabilizes over time. 
  • Understanding why fracture healing is impaired as people age and whether an already approved drug can promote healing14.



  1. 1RC1AR058405-01 -- Cortical Bone Porosity Identifies Diabetes Subjects with Fragility Fractures -- Link, Thomas M. (CA)
  2. 1RC1AR058162-01 -- Epidemiologic Study of Bone Marrow Fat and Osteoporosis -- Cauley, Jane (PA)
  3. 1RC2AR058973-01 -- GWAS in MrOS and SOF -- Orwoll, Eric S. (OR)
  4. 1R03AR056106-01A1 -- Identification of Gender Specific BMD Candidate Gene in Chromosome 1 -- Edderkaoui, Bouchra (CA)
  5. 3K08AR053566-03S1 -- Mechanisms of Non-Genomic Estrogen Signaling -- Robinson, Lisa J. (PA)
  6. 1RC1R058453-01 -- Implicit Learning in Osteocyte Network under Mechanical Loading -- Guo, X. Edward (NY)
  7. 1R03AR056827-01 -- Role of IGF-1 and Estrogen in Skeletal Anabolic Response to Loading -- Kesavan, Chandrasekhar (CA)
  8. 3R01AR053949-02S1 -- The Role of LRP5 in Bone Response to Mechanical Loading -- Johnson, Mark L. (MO)
  9. 1R03AR055738-01A1 -- Efficacy of Plyometrics to Increase Bone Mass in Men -- Hinton, Pamela S. (MO)
  10. 1RC1AR058389-01 -- Effect of Perinatal Diet on Developmental Programming of the Skeleton -- Bouxsein, Mary L. (MA)
  11. 1R15AR056858-01 -- Long-term skeletal effects of exercise during growth -- Warden, Stuart J. (IN)
  12. 1R01AR055927-01A2 -- Updating Skeletal Maturity Methods for US Children -- Chumlea, William Cameron (OH)
  13. 1R43AR056167-01A1 -- Calcium Phosphate Bone Cement Nanocomposites -- Lambert, Kenneth Lawrence (MO)
  14. 3P50AR054041-04S1 -- Translating molecular signal pathways to orthopaedic trauma care -- Rosier, Randy N. (NY)


 
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