Research: Bone Repair and Remodeling

 

Update 8/14/17: I have created a new illustration that summarizes some of the findings in this research. You can view it here under the title “Bone Remodeling”

A Proactive Approach to Osteoporosis Prevention:

Osteoporosis may not be inevitable for the informed individual. Bone is a dynamic organ that changes over time in response to age and external behaviors. Engaging in bone building/bone maintaining behaviors during childhood, adolescence and adulthood will decrease the likelihood of osteoporosis in later years. This research illustrates the mechanism by which exercise stimulates bone building. Perhaps an understanding of this mechanism along with an understanding of the modifiability of bone over a lifetime will result in a more proactive approach to osteoporosis prevention.

The interactive PDF that integrates all of the information below is available by clicking bone_health_fatunmbi

To experience the interactivity you will have to download the file to your computer.

Overview: Bone is a Dynamic, Living Organ that Undergoes Architectural Changes in Response to Environmental Stimuli

Bone is often characterized in ways that only highlight certain facets of its function. However, a focus on one facet of bone function and structure results in an incomplete understanding of this dynamic tissue. For example, thinking of bone primarily as a mineral repository will not help in the understanding of how physical exercise causes an increase in bone density and strength.

The purpose of this investigation is to create an interactive educational resource on bone health to enable an increased understanding of bone as a multifaceted organ for osteoporosis prevention.

The investigation aimed to accomplish this by establishing a clear connection between two factors: the changes that occur in bone architecture as a result of individual behavior, nutrition and exercise and the lifelong implications of these architectural changes in bone health. This interactive was reviewed by a content expert in the field of bone health for accuracy and efficacy.

Introduction: The Increasing Prevalence of Osteoporosis and Contributing Factors

The issue at hand is that despite its important role in the quality of life of Americans nationwide, bone health is declining rapidly as a result of the increasing prevalence of osteoporosis (Reginster, 2006)
Two possible reasons for this issue were identified:

  • A diminished perception of the modifiability and importance of bone health
  • Ambiguous connections between recommended activities to enhance bone health and the means by which they actually encourage bone health.

The target audience was medical school residents.

Research Question:

“How can a web-based interactive learning environment, that explores the dynamic nature of bone, be designed to increase a medical resident’s awareness of the importance of modifiable factors that influence or contribute to bone health?”

Designing for Learning and Knowledge Retention:

Three books informed the design of the interactive PDF. The book that was of the most practical use within the scope of this research was Design For How People Learn by Julie Dirksen.

book_1 book_3

The titles above:

  • E-learning and the Science of Instruction: Proven guidelines for consumers and designers of multimedia learning – Ruth Colvin Clark and Richard E. Mayer
  • Design For How people Learn – Julie Dirksen
  • Don’t Make me Think Revisited: A common sense approach to web usability – Steve Krug

Addressing Learning Gaps and Motivation

A gap may be defined as the space between where the learner currently is and where the learner needs to be. Four types of learning gaps are knowledge, skill, motivation and environment (Dirksen, 2012). Having a knowledge gap assumes that the learner is simply missing information. This study dealt with a knowledge gap.

Individuals are either extrinsically or intrinsically motivated to learn. The former requires external rewards and the latter learns for the enjoyment of learning.

Since appealing to extrinsically motivated learners is the more challenging of the two, this research considered design strategies for teaching extrinsically motivated learners.

Three design strategies used in this research are:

  • Avoiding extensive theory and background
  • Using interesting hypothetical problems to awaken intrinsic motivation
  • Intrinsic motivators- i.e the reward of mastering content (Dirksen, 2012)

Information Flow and Learner Feedback

In this study, common misconceptions about bone health are presented within the content. The learner is then prompted to answer qualitative questions about the content. The learner must reconcile the presented misconceptions with information presented in the interactive to produce a correct answer. The learner can then receive feedback about their answer by checking it against a presented ideal answer. This level of feedback fits within the scope of this research.

Levels of Learner Understanding

The levels of learner understanding, in increasing complexity, are:

  1. Remember
  2. Understand
  3. Apply
  4. Analyze
  5. Evaluate
  6. Create

Assuming that a learner may have only one exposure to the material presented in this interactive, the expectation of this study is that the learner would reach the “understand” phase. To reach the higher levels of understanding requires more time, feedback and practice beyond the scope of this interactive.

The presence of additional resources within the interactive caters to intrinsically motivated leaners in that they may explore all of the resources available to reach higher levels of understanding at their leisure.

Benefits of Storytelling

  • Information endures in memory
  • Familiarity in organization/easy storage (Dirksen, 2012).

The interactive web delivery asset in this research uses the story of Rosa, a 55-year-old Hispanic woman who is visiting the hospital because of a bone fracture. The point of the narrative is to inform Rosa about her bone health. This is achieved by answering Rosa’s questions which are embedded in the interactive.

The sequential nature of a story plays an organizational role for the reader. For example, the question “What types of exercises are osteogenic?” does not arise until it has been established that not only does bone respond and adapt to the strain that exercise exerts upon it, but this adaptation can be osteogenic. Information about Rosa’s life history is revealed throughout the story because characters make stories more interesting and engaging.

Benefits of Visuals

  • Engaging
  • Convey progressions well (i.e displaying healthy versus osteoporotic bone)
  • Decrease wordiness
  • Minimize cognitive overload
  • Provide context (Dirksen, 2012)

Literature Review

Bone structure: The three types of cells in bones are osteoblasts, osteoclasts and osteocytes.

  • osteoblasts (build bone)
  • osteoclasts (break down bone)
  • osteocytes (resident bone cells that assist in mechanotransduction)

Bones have a lacunae-canalicular network.

grbone2 (click image for source)

  • Lacuna (the cavity in which the osteocytes sit) are joined by interconnecting channels called canaliculi
  • The osteocytes’ cell processes live in this network of holes and tunnels.
  • With each osteocyte connecting with its neighbor and so forth, a functional syncytium is formed. This extensive interconnectivity creates a syncytium that serves to sense mechanical strains/forces (Tami, 2002).

Bone Is a Living, Changing Organ That Serves Many Functions.

skeleton_fatunmbi
Functions:

  • mineral reservoir
  • growth factor and cytokine depository
  • endocrine organ
  • acid base equalizer
  • detoxifier
  • house for marrow used for hematopoesis and fat storage (Fogelman, 2012)

Bone Participates in Modeling and Remodeling.

Modeling and remodeling are two processes by which the skeleton changes its shape, strength, architecture and size in response to the environment. Modeling occurs from childhood and adulthood and refers to the formation of bone in areas where it was not present. Remodeling is used to replace old, damaged or fatigued bone with new bone tissue. Remodeling maintains bone mass and the structural integrity of bone.

The focus in this study is on remodeling since, unlike modeling, this process continually renews bone throughout the lifespan long after skeletal maturity has been reached. The colored image below the graph is an illustration that was created to better visualize the stages of remodeling. The stages in the graph correspond to the colored illustrations below.

burr_and_allen_indiana_academic_press
(Burr, 2014)

fatunmbi_remodeling

Mechanical Loading and It’s Role in Bone Remodeling

fatunmbi_physical_activity

Mechanical loading is the prominent driving force in bone remodeling. In the absence of mechanical loading or usage, limbs will develop with only 30-50% of normal bone mass (Robling, 2009).

Mechanical loading is generated during physical activity as muscle contraction and ground reaction forces are transmitted through bone tissue. Remodeling can result in a gain or loss of bone. Bone loss can occur with overloading or with disuse.

Stress and Strain

robling_and_turner_bone_image

Strain is the magnitude of deformation in an object as a result of a force. There is certain level of elasticity within the material that is being acted upon up to a point (yield point). After the yield point, there is a transition zone in which the object deforms and does not bounce back to its normal shape upon removal of the force.

Added force beyond bone’s yield point, or repeated sub-optimal loading will ultimately result in a fracture of the bone.

Stress and strain can stimulate an osteogenic response in bone, but only within a certain range of force. When physical activity falls below a physiological minimal effective strain threshold, bone resorption will exceed bone formation (Bachrach, 2001).

Children and adolescents who engage in intensive weight bearing activity in childhood have been found, as adults, to have a significantly higher bone mineral density and volumetric bone density than their less active counterparts (Bachrach, 2001).

Mechanotransduction

Osteocytes are embedded in bone matrix. They are primary mechanosensors.
The sequence of events in mechanotransduction is as follows:

Mechanical loads > deformations > push osseous fluid > shear stress and drag forces on osteocyte membrane > forces perceived > cascade of signaling events > remodeling

mini_skeleton

mini_trabeculae   mini_histology

mini_syncytium

The first image above shows a physical activity that induces mechanical forces or loads upon bone via the tendons and ligaments. These forces then move through the internal anatomy and are transmitted all the way to the micro-anatomy of the bone.

The finer levels of anatomy are shown in the four remaining images. The second image shows the trabeculae or spongy bone that forms the inner layer of bones (Compact bone forms the outer layer of bones). The third image is a zoom in of  this trabeculae. The fourth image shows the cross-section of trabecule. The fifth image shows a zoom in of that cross section.

 (A)

 (B)

(A) After forces have been induced, they cause deformations within the bone matrix that push upon the fluid (highlighted green) found in the canals.

(B) This fluid moves across the membrane of the osteocyte processes. The processes perceive the forces and a cascade of signaling events that lead to remodeling occur.

Bone Remodeling

  

The signal cascade results in osteoclast recruitment. As shown in the first image above, an activated osteoclast (blue) secretes enzymes that dissolve the bone. As it moves across the bone it leaves behind a cavity. Eventually, the osteoclast departs and activated osteoblasts attach to the cavity filling it with new bone or osteoid (yellow). This osteoid will eventually mineralize to become mature bone.

Strain and Dynamic Loading

The two types of loading are dynamic and static. With dynamic loading, forces change quickly in magnitude and direction and have a shorter time interval. With static loading, forces are gradually applied and remain in place for a long period of time.

Dynamic loading is more osteogenic than static loading. This is because it causes a greater disruption in the canalicular fluid flow than static loading. This high level of disruption stimulates remodeling.

When comparing gymnasts to distance runners, the gymnasts had greater bone mass than distance runners. (Bachrach 2001). This is reflective of the larger ground reaction forces that are experienced and generated during gymnastics.

When comparing college swimmers to non-athletic control subjects, it was found that the swimmers had no greater bone mass than the non-athletic control subjects. This is likely because swimming is done in a weightless environment that doesn’t induce significant mechanical loads that would cause large disruptions in fluid flow.

  

Strength training (pictured above) is an example of dynamic loading.

Also, loading is most effective when it is interrupted by periods of rest.

Osteoporosis

Osteoporosis is characterized by:

  • Low bone mass and micro-architectural deterioration
  • Enhanced bone fragility (U.S. Dept. of Health and Human Service, 2004)

   
Normal vs. Osteoporotic bone (above image)

Osteoporosis can be primary or secondary in nature. Primary osteoporosis, also known as age-related osteoporosis, is the most common.

Osteoporosis is present in both sexes but is 2-3 times more common in women. This is in part due to the fact that women experience two periods of age-related bone loss. The first is rapid and begins at menopause. It tapers off into a slower continuous loss after four to eight years. Since men do not undergo menopause they do not have that first initial rapid loss of bone. They experience only the slow continuous loss. This translates into less bone being lost overall when compared to women.

Cost and Prevalence of Osteoporosis

prevalence_graph

The United States Department of Health and Human services states that by 2020, one in two Americans over age 50 will be at high risk for developing osteoporosis.

The cumulative cost of incident fractures is predicted to rise from 209 billion U.S. dollars (from 2006-2015) to 228 billion U.S. dollars (from 2016-2025) (Burge, 2007).

The cost of a second fracture is 834 million U.S. dollars with commercial insurance and 1.13 billion U.S. dollars with Medicaid (Burge, 2007).

The Problem

There are still many physicians who are either unaware of or less interested in osteoporosis because they think there is nothing you can do about it (Vecchione, 2004).

One study documented the care of 1,162 patients who were fifty-five years or older with a distal radius fracture (Freedman, 2000). Distal radius fractures are considered fragility fractures and are significant predictors of future hip fractures.

Of the 1,162 patients studied,

  • 33 or 2.8% underwent a bone density scan
  • 266 or 22% were treated with medications for osteoporosis and 20 women were given both interventions
  • 279 or 24% total of the 1,162 underwent diagnostic evaluation or treatment for osteoporosis

This study concluded that current physician practices might be inadequate for the diagnosis and treatment of osteoporosis in post menopausal women who have sustained a distal radial fracture (Freedman, 2000). This is only one of the studies found that support this viewpoint.

Both awareness and education are important in reducing osteoporosis because it is commonly called a “silent disease.” People with osteoporosis do not feel their bones getting weaker. According to the National Osteoporosis Foundation, breaking a bone is the first clue that osteoporosis may be present.

A Lifetime of Bone Health

Proactive or beneficial interventions can be applied at each life stage to foster life-long bone health. Please see the PDF for details on bone health at each stage and appropriate interventions.

Stages:

  • Childhood – Bone growth stage
  • Adolescence – Critical accrual stage
  • Adulthood – Maintenance stage
  • Midlife – Age related bone loss stage
  • Later years – Continued bone loss

A Pediatric Disease With Geriatric Consequences

rosa_and_relative Rosa (left), the patient in the interactive.

Osteoporosis had been called a pediatric disease with geriatric consequences. This is largely because a woman’s bone strength will be determined by the skeletal mass that she amassed within the first two decades of life.

Habits associated with the adolescent lifestyle predispose youth to osteoporosis in their older, later years. These habits include diminished milk consumption, increase in the intake of carbonated beverages, eating disorders, alcohol consumption and smoking (Hightower, 2000).

Learning objectives

The following questions from Design For How People Learn  were used to inform the creation of the learning objectives for the PDF created in this research.

  • Is this something that the learner would actually do in the real world?
  • Can I tell when they’ve done it?

I chose objectives that had practical applications and are readily observable.

Objectives:

  • Describe the ways in which bone is a dynamic, living and responsive tissue.
  • Identify the critical life-stage for osteoporosis intervention in terms of accruing bone mass.
  • Outline the steps between mechanically loading bone and the resultant osteogenic response.
  • Make age-specific suggestions to a patient about nutrition and osteogenic versus non-osteogenic exercises aimed at increasing bone health.

Methods

Overview:

Pre-production

  • Research and literature review
  • Identify current concerns
  • Storyboard a design solution

Production

  • Design layout concepts in inDesign
  • Organize content
  • Gather and create references for illustrations
  • Create illustrations
  • Embed links and add interactive elements

Post-production

  • Publish refined interactive on an online platform for public use.
  • Final paper.

Methods: Pre-production

Research relevant terms (listed below)

Identify current concerns: increasing prevalence of osteoporosis

Storyboard a design solution: Interactive PDF clarifying some ambiguity regarding the role of physical activity in the building of strong bones.

Terms and Subcategories That were Researched:
Osteoporosis: prevalence, cost, gender differences, prevention, current view, pathology.
Bone structure and Function: histology, adaptability, modeling and remodeling.
Mechanical loading: Strain rate and magnitude, osteogenic microstrain units, elasticity, plasticity, yield point, dynamic loading, static loading.
Mechanosensation: osteocyte processes, syncytium, lacunae-canalicular fluid flow, signaling.
Physical activity: impact on bone formation, overuse and disuse.
Bone health: stages of bone health over a lifespan, nutrition, modifiable and non-modifiable factors, critical cages for bone accrual, peak bone mass.
Design in learning: aesthetics, storytelling, learner engagement.
E-learning: multimedia design principles of effective e-learning, benefits and drawbacks.

Methods: Production 

Three concepts for the title page and the internal page were storyboarded in InDesign.

concept1a Concept A

concept1b  concept4c

conept2aConcept B

concept2b  concept2c

 Concept C

screen shot of research progress

The third was chosen and refined. Once the layout was established, the content was organized within it and interactivity was added. To achieve the goal of creating an interactive PDF that would not require flash to open, the interactivity options were limited. The interactivity in this research entails links to external sources within the PDF, forward and backward arrows for navigation and fly-out boxes that show and hide content in response to mouse hovers.

progress_organize_content

progress_interactivity

For the illustrations,  references were gathered, sketches were created and then transferred into Adobe photoshop for painting. Clicking on the references will lead to their sources.

ref_image1

progress_sketch  Sketchprogress_sketch_psdPhotoshop

Methods: Post-production

The interactive PDF was refined and completed along with the accompanying research paper.

post_prod_paper

Results

Here are five screen shots from the final interactive. The first one illustrates the interactivity of a the white fly-out box that shows when the mouse is hovered over the keyword “DEXA.”

Project Research by Dorothy Fatunmbi Project Research by Dorothy Fatunmbi Project Research by Dorothy Fatunmbi

Contributions

An interactive PDF that not only depicts the human skeleton as a dynamic and responsive organ, but also illustrates how external behaviors can build or degrade bone health.

The clarification of how physical activity impacts bone health.

An increase in a medical resident’s understanding may inform and enhance the quality of their patient education in addition to serving as a proactive approach to bone health and osteoporosis.

Limitations

Testing (this interactive has not been tested on individuals)
Building opportunities into the learning experience that allow for the acquisition of some proficiency before moving on to the next concept would have been a beneficial thing to integrate into the interactive. This was outside the scope of the project research

References

This is not an exhaustive list of the references used in this project research. These are the references that are cited in this blog page.

Bachrach, L. (2001). Acquisition of optimal bone mass in childhood and adolescence. Trends in Endocrinology & Metabolism, 12(1), 22-28

Burge, R., Dawson-Hughes, B., Solomon, D., Wong, J., King, A., & Tosteson, A. (2007). Incidence and Economic Burden of Osteoporosis-Related Fractures in the United States, 2005-2025. Journal of Bone and Mineral Research, 22(3), 465-475.

Dirksen, J. (2012). Design for How People Learn (pp. 1-191). Berkely: New Riders.

Freedman, K., Kaplan, F., Bilker, W., Storm, B., & Lowe, R. (2000). Treatment of osteoporosis: Are physicians missing an opportunity? The Journal of Bone and Joint Surgery, 82(8), 1063-1069.

Fogelman, I. (2012). Physiology of Bone Formation, Remodeling, and Metabolism. In Radionuclide and hybrid bone imaging (pp. 29-55). Berlin: Springer

Guede, D., Gonzalez, P., & Caerio, J. (2013). Biomechanics and Bone (1): Basic Concepts and Classical Mechanical Trials. Journal of Osteoporosis and Mineral Metabolism, 5(1), 43-50

Hightower, L. (2000). Osteoporosis: Pediatric Disease with Geriatric Consequences. Orthopaedic Nursing, 19(5), 59-62

Reginster, J., & Burlet, N. (2006). Osteoporosis: A Still Increasing Prevalence. Bone, 38, 4-9.

Robling, A., & Turner, C. (2009). Mechanical Signaling for Bone Modeling and Remodeling. Critical Reviews™ in Eukaryotic Gene Expression, 19(4), 319-338.

U.S. Department of Health and Human Service. (2004). Bone health and osteoporosis: A report of the Surgeon General. (pp. 1-404). Rockville, Md.: U.S. Dept. of Health and Human Services, Public Health Service, Office of the Surgeon General.

Vecchione, A. (2004, November 8). Surgeon General’s osteoporosis report wins wide support. Retrieved November 30, 2014, from http://drugtopics.modernmedicine.com/drug-topics/content/surgeon-generals-osteoporosis-report-wins-wide-support?page=full

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