Lessons From the Wrist

Research Summary

Topic: Assessed serum levels of 25-hydroxy vitamin D and protein markers of bone turnover to learn if knowing these levels could predict a patient’s risk for fragility fracture

Results: Understanding of whether vitamin D and bone turnover levels can predict a patient’s risk for fragility fracture

Patient Care application of results: Ability to determine which patients are most at risk for fragility fractures, allowing for preventative intervention with vitamin supplements and medications.

Simplified patient care application: Supplements and medications that can reduce the incidence of fragility fractures in patients who are most at risk.

Lessons from the wrist

OREF grant recipient looks for ways to predict risk and prevent fragility fractures

Jay D. Lenn

Fragility fractures result from a fall from a standing height or less and are not the result of high-energy trauma. They usually signify poor bone heath, and the incidence of such injuries increases significantly with age. Fragility fractures of the distal radius generally occur at an earlier age than fractures of the hip and spine¹.

“Wrist fractures may be a sentinel event,” stated Tamara D. Rozental, MD, orthopaedic surgeon at the Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School. “Fractures of the distal radius are usually the first fragility fracture, so they give us a unique opportunity to intervene, which might make a difference in preventing future injuries.”

A clearer picture of risk factors—especially modifiable risk factors of such injuries—may facilitate even earlier interventions. To that end, Dr. Rozental investigated serum levels of vitamin D and bone turnover markers in postmenopausal women with distal radius fractures.

Dr. Rozental’s work was underwritten in part by a 2012 Ruth Jackson Orthopaedic Society (RJOS)/Orthopaedic Research and Education Foundation (OREF)/DePuy Career Development Grant in Women’s Musculoskeletal Health. This program supports female orthopaedic surgeons who are working to improve knowledge in the area of women’s musculoskeletal health and enhance our understanding of gender and diversity differences in the outcomes of orthopaedic treatment. The amount of the award is $50,000 for up to one year.

A better understanding of risk

Decreased bone mineral density (BMD) is a well-documented risk factor for distal radius fracture, but this factor tells only part of the story. Fragility wrist factors occur among many people with normal BMD measurements². Therefore, there are likely other factors at work.

Vitamin D deficiency is strongly associated with hip fracture, and a small body of recent studies suggests that it may be associated with wrist fractures as well.³ Also, increased bone turnover is associated with an increased risk of fragility fractures, independent of BMD⁴, but the measurement of bone turnover risk factors is not standardized for the clinical assessment of risk.

In the OREF-funded investigation, Dr. Rozental, along with colleagues at the University of Connecticut Health Center, enrolled 255 women aged 50 or older, 105 of them with fragility wrist fractures and an age-matched control group of 150 women with no history of fractures before age 50. At the 3-month, post-treatment appointment, each fracture patient had a fasting blood draw to assess serum levels of 25-hydroxy vitamin D, as well as protein markers of bone turnover—three markers of bone formation and one of bone resorption. The 3-month delay in testing was intended to minimize the effect that the fracture itself may have on bone metabolism.

Secondary outcome measures included BMD and fracture severity using standard measures. Comparisons of the data from the fracture cases and controls enabled the researchers to determine whether:

• Vitamin D is a risk factor for distal radius fracture of fracture severity
• Bone turnover markers are predictive of fracture risk
• Levels of vitamin D are predictive
• Difference in vitamin D levels between fracture cases and controls are independent of possible differences in BMD

The researchers also measured serum parathyroid hormone (PTH), which plays a role in calcium regulation. Because vitamin D increases absorption of calcium in the intestines, a vitamin D deficiency may result in low serum calcium. Low calcium levels, in turn, trigger an increase in PTH, which pulls calcium from bone. The study, therefore, also enabled the investigators to examine the relationship among fractures, vitamin D, bone turnover markers and PTH.

Fracture prevention opportunities

The ultimate goal of understanding risk factors is the prevention of fragility fractures—identifying those people at risk, monitoring risk and, when possible, lowering the risk. Dr. Rozental stated, "If vitamin D deficiency ends up being identified as a risk factor, then I think we need to be more aggressive about monitoring that and supplementing people."

A better characterization of bone turnover markers may lead to the regular use of these measures in clinical practice. Dr. Rozental explained, "If we can determine a person's risk for fragility fractures because he or she has too much resorption or too little bone formation, perhaps we can better tailor medications."

Dr. Rozental’s study confirmed that a history of fracture and low BMD are strongly associated with distal radius fractures, but they are not the only factors that put patients at risk. They also found that postmenopausal women with distal radius fractures have similar levels of vitamin D but increased bone formation markers when compared to women without fracture. This suggests that monitoring vitamin D levels may not be as useful as previously thought in determining fragility fracture risk, but a bone formation marker, Serum type 1 procollagen (P1NP), may be a good indicator of bone fragility. These results were published in the October 2015 issue of The Journal of Bone and Joint Surgery⁵.

Funding research projects

The RJOS/OREF/DePuy grant was, according to Dr. Rozental, instrumental in getting this project off the ground.

“OREF’s reputation is one of its greatest strengths. Other than the National Institutes of Health (NIH) at the national level, every orthopaedic surgeon feels like OREF is the most prestigious orthopaedic research organization and foundation. When you think about getting research funding, an award from OREF is always highly regarded.”

Dr. Rozental described the necessity of preliminary funding, like what she received from OREF, for embarking on further investigations to identify other risk factors for fragility fractures, determine whether younger patients with fractures also have vitamin D deficiencies and better characterize the etiology of age-related bone alteration.

She said, "One of the reasons I like clinical medicine is because I'm making a difference one person at a time, and it's a very tangible thing. What research like this allows me to do is look at the big picture. This is a public health problem: osteoporosis affects millions of people every year. We hope the research makes a difference on a much larger scale."

Jay D. Lenn is a contributing writer for OREF. He can be reached at communications@oref.org

References:
1. Baron JA, Karagas M, BarrettJ, Kniffin W, Malenka D, Mayor M, Keller RB. Basic epidemiology of fractures of the upper and lower limb among Americans over 65 years of age. Epidemiology. 1996;7(6):612-8. Available at http://www.ncbi.nlm.nih.gov/pubmed/8899387. Accessed on May 2, 2016.

2. Oyen J, Gjesdal CG, Brudvik C, et al. Low-energy distal radius fractures in middle-aged and elderly men and women--the burden of osteoporosis and fracture risk: A study of 1794 consecutive patients. Osteoporos Int. Jul;21(7):1257-1267 Available at http://www.ncbi.nlm.nih.gov/pubmed/19813045. Accessed on May 2, 2016.

3. Oyen J, Apalset EM, Gjesdal CG, Brudvik C, Lie SA, Hove LM. Vitamin D inadequacy is associated with low-energy distal radius fractures: A case-control study. Bone. 2011 May 1;48(5):1140-5 Available at http://www.ncbi.nlm.nih.gov/pubmed/21295169. Accessed on May 2, 2016.

4. Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD. Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Miner Res. Oct 2005;20(10):1813-1819. Available at http://www.ncbi.nlm.nih.gov/pubmed/16160738. Accessed on May 2, 2016.

5. Rozental TD, Herder LM, Walley KC, Zurakowski D, Coyle K, Bouxsein ML, Wolf JM. 25-Hydroxyvitamin-D and Bone Turnover Marker Levels in Patients with Distal Radial Fracture: J Bone Joint Surg Am, 2015 Oct 21; 97 (20): 1685 -1693 Available at http://dx.doi.org/10.2106/JBJS.O.00313. Accessed on May 2, 2016.