Nonunions Diagnosis, Evaluation and Management

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We must find time to stop and thank the people who make a
difference in our lives.
—John F. Kennedy
First and foremost, I would like to thank my parents, Jagdish
and Kusum, for being extraordinary role models, as well for
their hard work and dedication to parenthood. They
have supported me throughout my life, both personally and
professionally. I am forever grateful. They continue to amaze me
now as grandparents.
To the most delightful, caring, and resilient children I could
have ever had. Thank you Priya, Deven, and Trevor for being so
understanding when I am on call or working late. You remind
me what is most important in life every time I look at you. The
three of you have been and continue to be my inspiration.
I want to thank those who have supported me professionally.
I am lucky to have trained at an institution with many “giants”
of orthopedics, and even more fortunate to have joined them as
a faculty member. They have always treated me as an equal,
despite having been my attendings. So thank you to Drs. James
Heckman, Charles Rockwood, and Fred Corley, who all
believed in me and gave me a chance. Thank you to those
that trained me during my orthopedic trauma fellowship, Drs.
Attila Poka, Robert Ostrum, and Brian Davison for making that
year of training educational, fun, and unforgettable.
Last but not least, I would be remiss if I did not thank my two
research mentors, Drs. Kyriacos Athanasiou and Mauli
Agrawal. They were instrumental in fueling my curiosity,
teaching me to write scientifically, and steering me towards
orthopedics. I wouldn’t be where I am today without their
encouragement and guidance so early in my career.
Animesh Agarwal, MD
Boerne, TX, USA
February 2017
Foreword

It is an honour to be invited to write the foreword to this important contri-

bution to the orthopedic surgical literature. This textbook is an extension
of the robust fracture information and knowledge base originally created in
the Department of Orthopedics at the Health Science Center in San Antonio
by Rockwood and Green in the 1970s. Despite many substantial advances in
primary fracture care over the last several decades, our ability to enhance
fracture healing has not improved very much; thus, delayed unions and
nonunions remain a common clinical challenge. Furthermore, as patients
develop greater expectations for very good or even perfect results after
injury, they are less willing to accept incomplete fracture healing as the final
outcome. Today’s patient wants to be able to return to high-level perfor-
mance following injury and not be sidelined because of a failure of fracture
healing. Therefore, when fracture healing does not occur, it is incumbent
upon the surgeon to identify the cause and develop an effective solution to
restore function in a timely manner. The textbook is a very useful resource to
that end.
Dr. Agarwal has compiled a very comprehensive overview of the causes
of and the effective treatments for virtually all of the common nonunion
patterns. His contributing authors are authoritative and recognized experts in
their respective fields, and the treatments for specific nonunions are presented
in a very comprehensive, well-illustrated, and user-friendly way.
This textbook clearly advances our understanding of the evaluation and
treatment of fracture nonunions, and it will be a very useful guide to the
surgeon who must find an effective means to restore function when the
normal fracture healing process has failed.

Manchester, VT, USA James D. Heckman, MD

March 2017

vii
Preface

An investment in knowledge pays the best interest.

—Benjamin Franklin

Nonunions have been a challenging aspect for orthopedic trauma surgeons.

The literature is scarce with recommendations for many of these problems.
The principles of nonunion management have been traditionally based on the
type of nonunion and its aetiology, whether it is a mechanical or biological
one. As orthopedic care has advanced with newer implants—such as locked
plating—old problems have been alleviated, but new issues have arisen as
well. Although patient factors and injury factors contribute significantly to
the development of nonunions, iatrogenic causes are not infrequent. Ortho-
paedic trauma care still requires attention to detail and the basic principles of
fracture management to help prevent the surgeon’s contribution to nonunion
development.
Over the last twenty years of my practice, nonunions have always been a
difficult problem to assess. New patient issues such as vitamin D deficiency
have come to light. Infection all too often accompanies nonunions and must be
evaluated. This text was designed to provide a single reference for the basic
principles of nonunion diagnosis, evaluation, and management. Although not
every single treatment option can be covered for every single anatomical area
and type of nonunion, we hope that this text is useful, not only for managing
these difficult problems but also in preventing nonunions from occurring by
avoiding surgical causes and mitigating patient risk factors.
The contributors to this text were selected based on their interest and
expertise in this subject. Nonunion management is unique in that it is rarely
taught; rather, surgeons have learned over the years through their own per-
sonal experience, oftentimes by trial and error. Learning a new subject,
technique, or gaining new knowledge requires the desire to be more
well-informed. To quote the great Woody Allen, “Eighty percent of success is
showing up”. The contributors have certainly shown up. If you are reading
this preface, we hope that you have taken a step towards “showing up”, and
thus being successful in the management of these difficult and challenging
cases.

Boerne, TX, USA Animesh Agarwal, MD

ix
Contents

1 Principles of Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Animesh Agarwal
2 Fracture Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Saam Morshed and Anthony Ding
3 Clavicle Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Laura A. Schemitsch, Emil H. Schemitsch
and Michael D. McKee
4 Proximal Humerus Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . 95
Ethan S. Lea and Philip R. Wolinsky
5 Supracondylar Humeral Nonunions . . . . . . . . . . . . . . . . . . . . . 115
Joseph Borrelli, Jr.
6 Nonunions of the Forearm . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Fred G. Corley and Ben S. Francisco
7 Nonunions of the Wrist and Hand . . . . . . . . . . . . . . . . . . . . . . 143
Matthew Lyons, Ahmad Fashandi and Aaron M. Freilich
8 Acetabular and Pelvic Nonunions . . . . . . . . . . . . . . . . . . . . . . . 183
Kyle F. Dickson
9 Proximal Femur Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Roman A. Hayda
10 Femoral Shaft Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Gil R. Ortega and Brian P. Cunningham
11 Distal Femoral Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Animesh Agarwal
12 Nonunions of the Tibial Plateau and Proximal
Tibial Metaphysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Thomas F. Higgins
13 Tibial Nonunions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Samuel E. Galle and David P. Zamorano
14 Distal Tibia and Ankle Nonunions . . . . . . . . . . . . . . . . . . . . . . 309
Kevin J. Pugh

xi
xii Contents

15 Special Techniques for Nonunions Associated

with Traumatic Bone Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Mark A. Lee and Michael P. Leslie
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Contributors

Animesh Agarwal MD Department of Orthopedics, Division of Orthopedic

Traumatology, UTHSCSA, San Antonio, TX, USA
Joseph Borrelli, Jr. MD, MBA Orthopedic Surgery, BayCare Medical
Group, St. Joseph’s Hospital-North, Lutz, FL, USA
Fred G. Corley MD Department of Orthopedics, University of Texas Health
Science Center at San Antonio, San Antonio, TX, USA
Brian P. Cunningham MD Department of Orthopedic Surgery, University
of Minnesota, Regions Hospital, St. Paul, MN, USA
Kyle F. Dickson MD, MBA Southwest Orthopedic Group, Baylor Univer-
sity, Houston, TX, USA
Anthony Ding MD Department of Orthopedic Surgery, San Francisco
General Hospital, Orthopedic Trauma Institute, University of California San
Francisco, San Francisco, CA, USA
Ahmad Fashandi MD Department of Orthopedics, University of Virginia,
Charlottesville, VA, USA
Ben S. Francisco MD Department of Orthopedics, University of Texas
Health Science Center at San Antonio, San Antonio, TX, USA
Aaron M. Freilich MD Department of Orthopedics, University of Virginia,
Charlottesville, VA, USA
Samuel E. Galle MD Orthopedic Trauma Service, Orthopedic Trauma &
Fracture Clinic, Saint Alphonsus—Boise Campus, Boise, ID, USA
Roman A. Hayda MD Rhode Island Hospital, Brown University Warren
Alpert School of Medicine, Providence, RI, USA
Thomas F. Higgins MD Department of Orthopedics, University Orthopedic
Center, University of Utah Health Sciences, Salt Lake City, UT, USA
Ethan S. Lea MD, MSc Department of Orthopedic Surgery, University of
California at Davis Medical Center, Sacramento, CA, USA
Mark A. Lee MD Department of Orthopedic Surgery, University of Cali-
fornia, Sacramento, CA, USA

xiii
xiv Contributors

Michael P. Leslie DO Department of Orthopedics and Rehabilitation, Yale

School of Medicine, New Haven, CT, USA
Matthew Lyons MD Department of Orthopedics, University of Virginia,
Charlottesville, VA, USA
Michael D. McKee MD, FRCS(C) Division of Orthopedic Surgery,
Department of Surgery, University of Toronto, Toronto, Canada
Saam Morshed MD, PhD, MPH Department of Orthopedic Surgery, San
Francisco General Hospital, Orthopedic Trauma Institute, University of
California San Francisco, San Francisco, CA, USA
Gil R. Ortega MD, MPH Department of Orthopedic Surgery, Mayo Clinic
Arizona Orthopedic Residency Program, Mayo Clinic Arizona, HonorHealth
Scottsdale Osborn Trauma Center, Scottsdale, AZ, USA
Kevin J. Pugh MD Orthopedic Trauma and Reconstructive Surgery, Grant
Medical Center, Columbus, OH, USA
Emil H. Schemitsch MD, FRCS(C) Division of Orthopedic Surgery,
Department of Surgery, University of Toronto, Toronto, Canada
Laura A. Schemitsch MA Division of Orthopedic Surgery, Department of
Surgery, University of Toronto, Toronto, Canada
Philip R. Wolinsky MD Department of Orthopedic Surgery, University of
California at Davis Medical Center, Sacramento, CA, USA
David P. Zamorano MD Orthopedic Trauma Service, Orthopedic Trauma &
Fracture Clinic, Saint Alphonsus—Boise Campus, Boise, ID, USA
 Principles of Nonunions
1
Animesh Agarwal, MD

There are however many factors to take into

1.1 Introduction
consideration such as the particular bone
involved, the specific anatomic regions of the
Fracture healing is a very unique process in the
particular bone, the fracture pattern, as well as
human body. Bone is a unique tissue in that it can
the method of treatment. There are certainly
regenerate itself during the process of healing. This
specific areas within the skeleton that already
requires a very complex process which is regulated
have a predisposition to impaired healing due to
by various metabolic and hormonal factors to
both biologic and mechanical factors such as the
include various growth factors. These biological
subtrochanteric femoral region. Additionally, the
processes occur at the cellular level requiring
treatment method may contribute to a nonunion
recruitment proliferation and differentiation of
due to the inadequate mechanical environment
many cells including endothelial cells, osteopro-
provided by the choice of fixation. Often times
genitor cells, platelets, macrophages, mesenchy-
the diagnosis is more retrospective in nature then
mal stem cells (MSCs), and monocytes. These
prospective. Nonoperative interventions such as
cells secrete various biologically active molecules
various noninvasive stimulation devices or
at the site of injury to facilitate fracture repair. The
medications can potentially augment the slow
bone morphogenetic proteins (BMPs) are
fracture healing process.
osteoinductive agents which promote the prolifer-
A delayed union may eventually heal or
ation and differentiation of undifferentiated cells to
eventually may become a nonunion. Often times
become either osteoprogenitor or chondroprogen-
it is difficult to diagnose a nonunion in real time,
itor cells. Although our bodies have the inherent
and much of the time the diagnosis is made ret-
capability to repair the fracture, the fracture healing
rospectively. If the process stops altogether, a
process can be impaired for numerous reasons.
nonunion has developed which may require
When the fracture healing cascade stalls, a
intervention. The US Food and Drug Adminis-
delayed union may develop, but the process may
tration (FDA) has defined a nonunion as a frac-
altogether cease. In a delayed union, both clinical
ture that is at least nine months old and has not
evidence and radiographic evidence of healing
shown any signs of healing progression for at
do progress, but it lags behind what the normal
least three consecutive months [1]. From a clin-
healing time should be for a particular bone.
ical perspective, we define a nonunion as one in
which the normal fracture healing process has
ceased, to the extent that, without further treat-
A. Agarwal (&) ment, healing will not progress. Thus, the
Division of Orthopedic Traumatology, Department
nine-month rule should not be applied to all
of Orthopedics, University of Texas Health Science
Center, San Antonio, TX, USA fractures and be based more upon the clinical
e-mail: [email protected] presentation and the individual patient [2].

© Springer Science+Business Media LLC 2018 1

A. Agarwal (ed.), Nonunions, DOI 10.1007/978-1-4939-7178-7_1
2 A. Agarwal, MD

In addition to a lack of clear-cut “time” guideli- scores. Long-bone nonunions had a utility score of
nes for a nonunion, there is difficulty in assessing 0.68 that was well below that of type-1 diabetes
a fracture for a nonunion based upon radiological (0.88), stroke (0.81), and HIV (0.79). Those with
findings and a wide disparity exists in orthopedic forearm nonunions had the worst quality of life.
surgeons’ perceptions of nonunion criteria and Unfortunately, even with successful treatment of
time points for nonunions [3]. Additionally, it is the nonunion, it has been shown that, at least in
well known that there are certain bones that are at respect to tibial nonunions, there is a long-term
a greater risk to go on to a nonunion. This may negative impact on one’s quality of life [9]. The
be due to the location on a certain bone due to indirect burden to society remains unanswered.
vascularity issues or the whole bone itself, e.g., It has been estimated that between 5 and 10%
scaphoid. In certain situations, the associated all patients will have some difficulty in healing
bone loss that occurs clearly exceeds any critical their fracture [6, 7]. It has also been reported that
size defect and will not heal with fixation alone, 1 out of 6 fractures that have delayed healing will
and thus, a nonunion is the expected result. It go onto a nonunion [10]. Additionally, the inci-
would be inappropriate to delay intervention in dence is also variable depending upon the ana-
these patients until 9 months per the FDA defi- tomic area in question. Unfortunately, the overall
nition. One can clearly see that the details of each incidence of delayed union and nonunion fol-
case must be taken into consideration when lowing fractures has been thought to be increas-
deeming it a nonunion. ing due to various factors including an aging
There has been considerable discussion population, increased obesity, diabetes, smoking,
regarding the costly burden of nonunions finan- vitamin D deficiency, as well as improved sur-
cially, but the affects on functional outcome and vival rates of patients with multiple injuries.
the quality of life can be devastating. In a study of These aforementioned factors certainly affect the
tibia nonunions, the authors found that these biological aspect of fracture healing; however,
patients had high per patient costs overall with the mechanical aspects of fracture healing can
increased healthcare resource usage [4]. In a study also be problematic. The mechanical factors are
by Kanakaris and Giannoudis [5], the increased often dependent upon the type of treatment
costs were also associated with humeral and method chosen by the surgeon in discussion with
femoral nonunions in addition to tibia nonunions. the patient. The mechanical stability that can be
Not only are there direct costs associated with the achieved at the fracture site is dependent upon
treatment, but also significant indirect costs the type of stabilization method used whether it
associated with losses in productivity [6]. Earlier be nonoperative or operative means. Cast stabi-
treatment based on earlier diagnosis could result in lization of the fracture has the least amount of
significant financial savings to the healthcare stability, but can be effective in many fractures
system and society. In addition to the additional that are amenable to nonoperative management.
cost, there are significant impacts to the quality of Methods of surgical fixation include open
life and functional outcome of these patients. In a reduction and internal fixation, external fixation,
study evaluating patients that have tibial shaft and intramedullary nailing. This multitude of
nonunions with functional outcome scores, Brin- options can lead to a vast spectrum of stability.
ker et al. [7] found that the SF-12 scores (physical This affects the type of fracture healing that can
and mental) indicated an extremely disabling occur, either primary or secondary fracture
effect on physical and mental health. The impact healing, in which callous formation occurs in the
on physical health was comparable to that of latter type. The interplay of biologic factors,
end-stage hip arthrosis and worse than congestive including osteogenic cells and the extracellular
heart failure. In a follow-up study, Schottel et al. matrix, which acts as a natural scaffold, and
[8] found that all longbone nonunions had a very growth factors inherent to fracture hematoma
low health-related quality of life based upon Time along with the mechanical environment forms
Trade-off direct measures to determine utility the basis of the diamond concept of fracture
1 Principles of Nonunions 3

healing introduced by Giannoudis et al. [11]. All the risk of complications. A thorough and com-
of these factors should be taken into considera- plete physical examination should be performed
tion in the management of nonunions as well. on all patients presenting with a nonunion. The
Neglect of one of these key cornerstones of physical examination should include a general
fracture healing can doom the treatment of the physical which may point to other underlying
nonunion. disorders that may have been overlooked.
Many people have tried to elucidate factors, Detailed examination of the extremity involved
biological markers, or other aspects of the frac- should be performed to include an evaluation of
ture or treatment that could contribute to a non- the neurovascular status, looking for open
union allowing one to potentially predict which wounds (draining sinuses), healed lacerations
fractures or which patients may progress on to a (indicative of perhaps an open injury), healed
nonunion [12–30]. The establishment of a non- incisions, clinical alignment, joint motion, and
union on radiographs does not necessarily imply examination of the presumed nonunion site for
the need for operative intervention. Nonunions motion. Any open wound or draining sinus in
maybe asymptomatic, and therefore, both clinical proximity to the fracture should lead one to
and radiological findings as well as the patient’s suspect a septic nonunion and is so until proven
current function and wishes are necessary to otherwise. Such open wounds must be taken into
determine the best course of action in the man- consideration, and a soft tissue reconstruction
agement of a nonunion. Surgical intervention of plan will need to be integral to the overall bony
the original fracture can often times make the reconstruction. Previous incisions may limit
diagnosis of a nonunion difficult especially in the options and may dictate how previous hardware
absence of associated hardware failure. Thus, the is removed. Alternative approaches may need to
evaluation, diagnosis, and the treatment of a be employed if the existing soft tissues are
nonunion can be very complicated [10, 31]. It scarred in or suboptimal for further surgical
requires a thorough understanding of the original intervention. If there is a deformity, correction of
injury and treatment, subsequent treatments as the malalignment has to be taken into consider-
well as patient comorbidities, which may have ation as well. This includes any leg length dis-
contributed to the development of the nonunion. crepancy that may need to be addressed. Joint
motion may be limited from arthrofibrosis or a
result from a false joint at the nonunion site, or
1.2 History patients may have developed contractures. Any
surgical plan must take into consideration the
Evaluation of a nonunion should begin, first and need for lysis of adhesions, soft tissue releases,
foremost, with an evaluation of the patient and etc., to insure the best possible overall outcome.
their medical history. A thorough evaluation and In short, preoperative planning taking all these
review of the patient’s past medical and surgical factors into consideration before going down the
history including medications are very important reconstructive pathway is paramount.
in helping to elucidate the etiology of the non- It is extremely important to obtain an accurate
union. It is important to take a medical history history of the original injury mechanism as well
and assess for vascular disease, malnutrition, as other fracture characteristics. It is important to
diabetes, social history, and metabolic bone dis- determine whether or not the fracture was from a
ease such as osteoporosis, endocrine disorders, high-energy or low-energy injury. The extent of
vitamin D deficiency, hepatic and renal disor- the initial soft tissue injury as well as the amount
ders, steroid use, and rheumatologic disorders. of periosteal stripping that may have been
Many of these comorbidities will be discussed encountered at the time of surgery or because of
below under “etiology.” Social issues such as the surgery may shed light on the potential cause
smoking or illicit drug use are important to note of the development of the nonunion. It has been
as these things may prevent healing or increase recently suggested that compartment syndrome
4 A. Agarwal, MD

and associated fasciotomy may be a risk factor 1.3 Risk Factors for Nonunion
for the development of nonunion in tibia frac-
tures [12]. Open fractures obviously have much Biological factors and mechanical factors can
more soft tissue damage, and the potential for an contribute to the development of a nonunion.
occult infection and septic nonunion must also be These can be related to the patient or the inter-
taken into consideration. vention performed by the surgeon. If the patient
A careful evaluation of all previous surgeries has been referred in, as mentioned previously, it
is critical, especially the index operation. Review is helpful to obtain previous injury radiographs,
of the operative reports and/or injury radiographs computed tomography (CT) scans, and other
along with the immediate postoperative films can imaging studies as well as operative reports to
be crucial to understanding the underlying cause. understand what was done and why it was done.
Subsequent interventions should also be evalu- If you are the index surgeon, it is important to
ated in a similar manner, taking into considera- critically asses your own surgical intervention to
tion the pre- and post-op radiographs and the determine whether things that were done may
details of the surgical procedure. If bone grafting have contributed to the nonunion. Decision
or biologic adjuncts had been done or used at any errors can always occur, and what is successful in
time, the type of bone graft or adjunct, the one patient may not be so in another patient. In
location of harvest of the autogenous bone graft, any event, risk factors for the development of a
should be noted. Previous sites of harvest may nonunion can be classified as patient dependent
limit future options. Inadequate fixation or or independent [10, 25]. Many of the indepen-
extensive surgical exposures can be large deter- dent factors are more surgeon-dependent factors
minants in the development of a nonunion. In or injury characteristics.
fractures treated with intramedullary nails, ex- The injury characteristics unique to a specific
ternal fixation, cast stabilization, or bridge plat- fracture location will be discussed in each specific
ing, a relatively stable construct has been created anatomic section, but some generalities can be made.
allowing for callous formation. In cases of open Areas that are known to have tenuous blood supplies
reduction and internal fixation (ORIF), an envi- have been shown to be at risk of nonunion [10, 28,
ronment with absolute stability often is created 32]. Such areas include the femoral neck, sub-
allowing for primary bone healing without cal- trochanteric region of the femur, the scaphoid, the
lous formation. The surgical assault obviously talus, the metadiaphyseal region of the fifth meta-
affects the amount of soft tissue stripping which tarsal, and tarsal navicular body. Open fractures with
can affect the amount of blood supply to the their significant soft tissue stripping clearly have
fracture site. Additionally, past surgical inter- increased risks of nonunion as well as infection [23,
ventions and hardware that is present can cer- 25, 26, 28, 29]. The associated soft tissue injury and
tainly affect future treatment options for the muscle loss in severe open injuries can result in loss
management of the nonunion. of the blood supply to the bone resulting in a detri-
A thorough evaluation of prior complications mental effect on the healing process and increasing
should be performed. Any history of infection the risk of infection. Lin showed that functional
should increase one’s suspicions for continued outcomes in patients with open tibia fractures were
infection even in the absence of clinical signs or worse than those with closed fractures [33]. West-
symptoms. Nerve injuries should be assessed as geest et al. [29] found that fractures which were
this may limit the overall outcome of any non- classified as open grade IIIA injuries were associated
union reconstruction and may lean one toward a with delayed healing and nonunion. Additionally, in
more definitive intervention such as amputation. this prospective cohort of 736 subjects, all with open
Previous vascular injuries may require further long bone fractures, deep infection was associated
assessment in terms of viability of the previous with delayed healing and nonunions. In a retro-
repair and a thorough assessment of the vascular spective study of long-bone fractures treated with
status of the limb. intramedullary nailing, Malik et al. [23] found that
1 Principles of Nonunions 5

open fractures had a significant association with the stabilization affects gene expression involved in
development of deep infection which also was fracture healing. Relative stability constructs
associated with the development of a nonunion. In such as intramedullary nailing, cast immobiliza-
the same study, they alluded that opening of a closed tion, and external fixation allow the fracture to
fracture also was a significant contributor to the heal by callus formation; however, excessive
development of a nonunion, and therefore, opening motion could lead to a hypertrophic nonunion.
of the fracture, in cases of intramedullary nailing, be The rigidity of the fracture fixation has been
avoided if possible. In the study by Blair et al. [12], shown to improve the process of healing [37].
fasciotomy for compartment syndrome in tibia Reaming of the canal in intramedullary nailing
fractures, which in essence is opening of the fracture, can increase the size of the nail and enhance the
was also associated with significant increase in both mechanical stability. The effect of reaming has
infection and nonunion. In an effort to prevent been looked at extensively [39]. It has been well
infection in open fractures, it is well established that established that reaming enhances fracture heal-
antibiotics be administered as rapidly as possible and ing and that there is a higher incidence of delayed
hopefully within an hour of the fracture presenting union and nonunions in unreamed nails with
[34]. Often times the open fractures are also associ- more secondary procedures to obtain union [23].
ated with significant bone loss and in most cases This is true despite a recent study showing that
such defects cannot heal on their own and are the functional outcomes in tibia fractures were
expected to become nonunions if left alone. These not affected by reaming [33]. Inadequate internal
eventually will require bony reconstruction. The fixation when one is trying to achieve absolute
type of reconstruction, timing of bone graft place- stability to create an environment for primary
ment, and the source of bone graft is highly variable bone healing can also lead to excessive motion
among orthopedic trauma surgeons [35]. Deter- and a subsequent nonunion. Niikura et al. [25]
mining the amount of bone graft for such defects can reviewed 102 nonunions of which almost 80%
be problematic, and some have tried to develop were related to or solely caused by inadequate
quantitative models to determine the amount needed stability or reduction. Conversely, rigidly fixing
[36]. Other fracture characteristics that need to be fracture fragments with gaps or without proper
assessed include the degree of displacement, the internal fixation techniques such as obtaining
extent of comminution, the amount of cortical compression across fracture planes may delay or
apposition at final fixation, and the stability of fixa- even prevent healing [31]. Fixation can be too
tion [24, 25, 28, 32, 37, 38]. rigid leading to a failure in healing. If the patient
Surgeon factors can contribute to either bio- had undergone what was felt to be appropriate
logical reasons for the development of a non- fixation with appropriate surgical technique for
union or a mechanical one [23, 25, 28, 32]. the fracture in question, then it is important to
Contributions to a biological cause include investigate patient-related factors, both biological
excessive stripping of soft tissues, failure to bone and mechanical, that may have contributed to the
graft at the appropriate time, and inadequate development of the nonunion. Brinker et al. [13]
debridement of devitalized/dead bone, which can created an algorithm on when to refer patients for
lead to infection, which then may prevent union. endocrine workups in relation to their nonunion.
Mechanical factors introduced by the surgeon are When evaluating the nonunion, the technical
related to the method of treatment and/or implant aspects of the fracture fixation should be asses-
for the original fracture. Fracture stabilization has sed. If there was no technical error, then it was
significant affects on fracture healing. In a liter- suggested that perhaps there was a metabolic
ature review by Hildebrand et al. [37], the type etiology to the nonunion, and thus, the patient
and timing of fracture stabilization can alter the should be referred to an endocrinologist. If
systemic inflammatory response after trauma technical error was a crucial factor in the
and can affect fracture healing. They also found etiology, referral was not indicated. However, it
that the type and stability of the fracture is important to still assess metabolic issues even
6 A. Agarwal, MD

in light of inadequate fixation as many patients fixation techniques may need to be employed to
still have some deficiencies in bone metabolism obtain improved fixation by the judicious use of
[13]. locked, fixed angle, or load-sharing devices such
Patient factors contributing to mechanical as intramedullary nails when appropriate.
problems can be related to noncompliance with Patient medical factors contributing to a bio-
weight-bearing restrictions or an error in allow- logical cause for the nonunion are many and can
ing the patient to weight bear too early. The be problematic not only from the original fracture
healing process is always a race between hard- standpoint but also for the treatment of an
ware failure and fracture healing, and thus, when established nonunion [10, 13, 25, 32, 40].
patients present with a nonunion in conjunction Established diseases such as vascular disease,
with hardware failure, the time from the original rheumatologic disease, and s/p organ transplan-
surgery is important in determining what came tation cannot be affected, but their effects on
first—the hardware failure or nonunion, as each fracture healing and subsequent management of
one can lead to the other. Often times, with plate the nonunion need to be taken into consideration.
failure there is an associated deformity through Perhaps their steroids or immunosuppressive
the nonunion site (Fig. 1.1). In cases of early agents can be held for short time period which
hardware failure, often times the patient has would allow for surgical intervention and heal-
started weight bearing too early or was allowed ing, and such decisions should be made in con-
to do so. This is more common in cases of plate junction with the patients’ appropriate other
fixation. In these situations, the fracture has not physicians. A multidisciplinary approach is nee-
healed sufficiently to handle the body weight and ded to get many of these patients healed.
the implant is taking all the stress leading to early Although there are many endocrine abnor-
failure. Failure can be in the form of screw malities that can affect the musculoskeletal sys-
loosening, implant breakage, or bending. tem, such as thyroid and parathyroid disorders,
Depending on the fracture pattern and amount of hypogonadism, and calcium imbalances to name
comminution as well as the location, it may still a few [13], diabetes has had the most attention
unite. In the lower extremity more so than the due to the high prevalence in the population.
upper, the alignment may gradually worsen as Diabetes has been shown to prolong healing
stability is lost and a mal-aligned nonunion can times for fractures [40, 41]. It is also well doc-
develop. In some instances, especially where umented that patients with diabetes have
there is comminution, as the angulation worsens increased complications when dealing with
resulting in more bony contact, the fracture may musculoskeletal conditions, especially with
unite resulting in a malunion. In late cases of fractures [32, 42, 43]. In a nationwide population
hardware failure, the fracture may have healed based study out of Taiwan, diabetics were found
sufficiently to handle some weight in addition to to have an increased incidence of fractures as
the implant and may have maintained the align- well as more adverse events and a higher mor-
ment. After a while, the implant undergoes fati- tality after fractures [42]. The addition of neu-
gue failure as the micromotion from the loading ropathic complications can make even simple
leads to failure of the implant at a stress riser fractures that require surgery end up being dis-
such as a hole in the plate. The alignment is often astrous for the patient. Wukich et al. [43] showed
times maintained, but the patient has pain and that patients with ankle fractures that had com-
discomfort which necessitates surgical interven- plicated diabetes had a 3.8 times increased risk of
tion. Loss of fixation can also occur without overall complications and a 3.4 times increased
weight-bearing issues. This is often the case in risk of malunion and nonunion compared to
patients with poor bone quality such as in those uncomplicated diabetic patients. These patients
with comorbidities such as diabetes or osteo- were also 5 times more likely to require revision
porosis. It is important to know whether patients surgery or arthrodesis. Diabetics need to under-
have these conditions as special surgical and stand that glucose control is extremely important
1 Principles of Nonunions 7

Fig. 1.1 Patient with right

ankle injury treated with open
reduction and internal fixation
of fibula and closed treatment
of distal tibia fracture.
Referred for nonunion after
progressive deformity
developed. a–c Three views
(anteroposterior [AP],
mortise, lateral) of the right
ankle show failure of the
fibula hardware and
mal-alignment with nonunion
of both the tibia and fibula.
Patient underwent hardware
removal and cultures. d–
f Three views (AP, lateral,
and mortise) of the right ankle
after hardware removal. Due
to the malalignment and stiff
nonunion, a Taylor spatial
frame (TSF) was applied to
allow correction and healing
of the nonunion. g–h AP and
lateral after TSF applied to
right ankle prior to correction.
i–j AP and lateral with TSF
showing full correction of the
deformity and realignment of
the limb. k–m Three views
(AP, lateral, and mortise) of
the right ankle 1 year after
consolidation of nonunion
and removal of TSF
8 A. Agarwal, MD

for them to avoid diabetic complications of end supplementation in all fracture patients, the cost
organ damage, neuropathy, nephropathy, and of an 8-week course of treatment was determined
peripheral arterial disease to minimize further and compared to the cost savings assuming just a
musculoskeletal complications [32]. Diabetics 5% reduction in nonunions. This would result in
should be treated with prolonged immobilization a potential cost savings of $65,866 annually [47].
and delayed weight bearing compared to the Many dosages of replacement therapy are avail-
nondiabetic to aid in avoiding complications. able, but the authors’ preference is for high-dose
Additionally, many of these patients require (50,000 IU) vitamin D weekly for six months
additional fixation for otherwise straightforward along with calcium supplementation. The target
fractures to try and prevent the late complications is to obtain a 25-OH level in the 40–60 range.
that occur with these injuries. Patients with low vitamin D can also develop
Vitamin D deficiency or insufficiency has secondary hyperparathyroidism and should also
been linked to nonunions, but a clear causal link have a parathyroid hormone (PTH) level drawn
is difficult to establish [13, 40]. Both the 25-OH when evaluating for a nonunion. The high PTH
vitamin D and 1, 25 OH2 vitamin D levels can be can contribute to the development of a nonunion
monitored, but the 25-OH level is the one that [13]. In most cases, the high PTH will resolve
is important. Patients with 25-OH levels <20 are with appropriate vitamin D replacement therapy.
considered insufficient and between 20 and 30 Osteoporosis has also been linked to the de-
deficient. It is not clear however whether higher velopment of nonunions [32]. The issues with
levels than simply above the 30 level are needed osteoporotic bone healing are both biologic and
in patients with fractures. Brinker et al. [13] mechanical [48]. By definition, osteoporotic
showed that a preponderance of their nonunion bone is bone with less bone mass and as such is
patients had vitamin D deficiency. They had 37 at an increased risk for fracture. The biologic
patients that were evaluated for a metabolic or changes that occur with osteoporosis, including a
endocrine abnormality of which 68% (25 of 37) diminished level of mesenchymal stem cells and
had vitamin D deficiency. It has become thus osteoblasts, a decrease in the chondrogenic
increasingly clear that many patients are vitamin potential of the periosteum and other alterations
D deficient or insufficient. In a meta-analysis of in the fracture healing pathway results in a less
the literature, it was found that the pooled than robust fracture healing process [32, 40, 48].
prevalence of hypovitaminosis was 77.5% in Additionally, because of the lower bone mass,
young trauma patients and 73% in geriatric fra- the fixation in such bone can be problematic and
gility fracture patients [44]. In a follow-up study, as such can lead to inadequate fixation and
the same authors showed that there is a lack of fracture stability. The result can be a nonunion.
consensus in prescribing vitamin D to fracture Many specialized techniques have been descri-
patients. They found that 66% of surgeons ten- bed in the management of osteoporotic fractures
ded to prescribe vitamin D to fragility fracture and should be employed when dealing with
patients compared to 25.7% to nonfragility nonunions especially if mechanical failure was a
fracture patients [45]. The lack of prescribing in significant contributor to the development of the
this population needs to be re-examined since the nonunion. Locked plating, use of load-sharing
prevalence of low vitamin D in young trauma devices, use of fixed angle devices, augmentation
patients is high. Low vitamin D is more prevalent of fixation with cement or bone graft substitutes,
than previously thought and is widespread in adjunctive use of structural bone grafts, and
patients of all orthopedic subspecialties and not preservation of soft tissue can assist in the
just orthopedic trauma [46]. Management of management of these fractures and nonunions
vitamin D is easily done via replacement therapy [48]. Although most osteoporotic individuals are
and has been shown to be successful in raising elderly, age is an independent factor which can
serum levels [44]. In a study to evaluate the cost negatively affect fracture healing also resulting in
benefit of both calcium and vitamin D delayed unions or nonunions [49]. This decline