Published 7/1/2016
Laura Bruse, MD

Big Data Supports Benefits of Sexual Dimorphism Research

The AAOS Women's Health Issues Advisory Board (WHIAB) seeks to advocate, advance, and serve as a resource for research on sex and gender differences in musculoskeletal health for a variety of audiences, including orthopaedic surgeons, policymakers, and the general public. However, many orthopaedic surgeons may ask, "Why should musculoskeletal research efforts direct resource dollars to sexual dimorphism?" The answer is "Big Data."

Data's impact
The Society for Women's Health Research (SWHR) is a national nonprofit organization widely recognized as the thought-leader in promoting research on biologic differences in disease. This year, the topic of SWHR's annual event in Washington, D.C., was "Revolutionizing Healthcare & Research Through Data."

The AAOS WHIAB supported the event, which benefitted science, advocacy, and educational programs designed to ensure that women's health remains a priority in this nation. In particular, it drew attention to the many ways in which science and basic research can revolutionize the delivery of medical care based on sexual dimorphism data. Some diseases and conditions affect women (females) disproportionately, a fact that is becoming more apparent as science and clinical studies uncover the effect sex has on normal development, growth, diseases, and musculoskeletal conditions.

As a result of SWHR's efforts over the last 25 years, the study of sex differences in disease has reached a wider audience, with an increased number of women and minorities participating in clinical trials. SWHR has successfully increased federal funding for biologically based research, won the passage of notable legislative changes, and put women's health at the forefront of research.

Providing proof that data can transform medicine, medical research is continuously revealing an understanding of differences and similarities in males and females and the application in disease processes and treatment. Accordingly, an increasing number of major medical research institutional studies now consider sex a variable in their research, and in 2014, the National Institutes of Health (NIH) announced it would distribute $10.1 million in grants to medical research scientists with the goal of countering gender bias in studies.

The belief that sex differences exist in healthy cells, tissues, and organ biology is changing the practice of medicine. Males and females may respond differently to medication, treatment, and management, which translates into different outcomes. The need to transform this knowledge into applicable principles tailored individually to male and female patients—and to share these treatment principles—will help to change the future of health care.

Sexual dimorphism in orthopaedics
Osteoporosis and osteoarthritis (OA) are major musculoskeletal conditions that demonstrate dimorphism over the lifespan. Response to treatment for these conditions between males and females is different. For example, research in knee arthritis demonstrates the following differences:

Mobility factors

  • A history of knee injury is a stronger risk factor for males.
  • Quadriceps weakness raises the risk of knee OA by increasing the load transmitted to the knee joint, affecting females more than males.
  • Females have thinner knee cartilage and lose knee cartilage at faster rates than males.

Response to therapy

  • Mobility and function prior to total knee arthroplasty has been found to be worse in females compared to males.
  • Mobility improves for both sexes following surgery, but females do not reach the same functional level as males.

The role of hormonal influences on the development of knee OA

  • Female human articular chondrocytes may function better when estrogen is available.
  • Male human articular chondrocytes are more responsive to vitamin D metabolites.
  • Vitamin D receptors and mRNA for inflammatory cytokines are differentially expressed in degenerated cartilage in a sex-specific fashion.
  • Subchondral bone osteoblasts exhibit sex-specific responses to estrogen.

Leptin, adipose tissue, and OA

  • Obesity affects females more than males.
  • Females with OA have higher leptin levels in synovial fluid than males with OA.

Looking to the future
Supported by big data, sex-specific research will increase, and with it, movement toward sex-specific delivery of treatment and care in orthopaedics. With each successfully completed research project, new information is uncovered. The future includes, and consumers will call for, the best practice management of sex-based healthcare delivery.

As time goes on, clinical practice, evaluation, management, treatment, and basic science research will continue to identify and confirm what many of us already know: sexual dimorphism exists in musculoskeletal medicine and there are data that prove it.

I encourage orthopaedic researchers and clinicians to consider sex differences when planning research, reporting results, and providing clinical or surgical service. Observe, look at evidence, become aware, and translate your findings into clinical practice. Be conscious of bias in yourself and others. Your efforts will help ensure that important work related to women's health care continues.

For more information on SWHR, visit www.swhr.org

Laura Bruse, MD, is chair of the AAOS Women's Health Issues Advisory Board.

Putting sex in your orthopaedic practice
This quarterly column from the AAOS WHIAB and the Ruth Jackson Orthopaedic Society provides important information for your practice about issues related to sex (determined by our chromosomes) and gender (how we present ourselves as male or female, which can be influenced by environment, families and peers, and social institutions). It is our mission to promote the philosophy that male and female patients experience and react to musculoskeletal conditions differently; when it comes to patient care, surgeons should not have a one-size-fits-all mentality.