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Case Reports in Endocrinology

Volume 2015, Article ID 670809, 7 pages
http://dx.doi.org/10.1155/2015/670809

Case Report
Characteristics and Treatment Results of 5 Patients with
Fibrous Dysplasia and Review of the Literature

Nilufer Ozdemir Kutbay,1 Banu Sarer Yurekli,1 Emine Kartal Baykan,1

Serap Baydur Sahin,2 and Fusun Saygili1
1
Endocrinology Department, Ege University Faculty of Medicine, Izmir, Turkey
2
Endocrinology Department, Recep Tayyip Erdogan University Faculty of Medicine, Rize, Turkey

Correspondence should be addressed to Nilufer Ozdemir Kutbay; nozdemirkutbay@hotmail.com

Received 10 January 2015; Accepted 1 June 2015

Academic Editor: Suat Simsek

Copyright © 2015 Nilufer Ozdemir Kutbay et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Aim. Fibrous dysplasia is a rare bone disease caused by missense mutation leading to abnormal fibroblast and osteoblast proliferation
and increased bone resorption. FD can present in monostotic or polyostotic forms. About 3% of FD could be in association with
McCune-Albright syndrome (MAS). Because FD is a rare disease, there is limited data in the literature about characteristics of
disease and response to treatment. Methods. We present our five cases of FD with general properties and their responses to medical
treatment. Results. Two of our patients had polyostotic and three had monostotic FD. One of the polyostotic patients had MAS.
One of our patients had surgery for femur fractures, facial asymmetry, and findings of compression. Four patients were given
pamidronate; one was given zoledronic acid as bisphosphonate treatment. Bone pain was relieved in all patients with medical
treatment. Conclusion. There was a decrease in bone turnover markers to some degree with medical treatment but no radiological
improvement was observed.

1. Introduction monostotic form with one bone site or in polyostotic form

with multiple bone sites. Monostotic forms compromise 70–
Fibrous dysplasia (FD) is a benign bone disease which has 80% of FD; rest of FD mostly consists of polyostotic forms
genetic noninheritable origin. FD occurs due to missense [2].
mutation in gene coding for the 𝛼 subunit of the stimulatory
Many patients have limited bone involvement with no
G-protein, Gs, in the GNAS complex locus in chromosome
symptom or bone pain, but the disease can cause significant
20q13. As a result of these GNAS mutations, abnormal
disabilities like bone deformity and neurologic compres-
proliferation and differentiation of bone marrow stromal
cells lead to fusiform fibroblast-like cells. Those cells create sions [2]. Some patients have endocrine abnormalities and
poorly differentiated osteoblasts [1]. Abnormal bone in a hyperpigmentation of the skin so-called McCune-Albright
fibrous stroma results in increased bone resorption with the syndrome (MAS) [6].
hyperactivity of osteoclastic cells [2]. There is no spontaneous resolution of FD. Not all patients
FD is a rare bone disease leading to bone pain, deformity, require treatment. Surgery may be indicated if bone defor-
and fracture. It is common that FD could be a silent disease. mity is large and causes compression of adjacent tissue.
FD was first described by Lichtenstein in 1938 [3]. It has been Bisphosphonates are often used as medical treatment as they
estimated that the prevalence may be around 1/30.000 [4]. may reduce the increased bone resorption [6]. Because of
Men and women are equally affected [2]. It is benign, slowly the fact that FD is a rare disease, a few published data are
progressing disease and especially involving craniofacial available. Herein, we present our five cases of FD with clinical
skeleton, long bones, and costa [5]. FD can present in properties and medical treatment results.
2 Case Reports in Endocrinology

(a) (b)

(c)

Figure 1: Radiologic images of patient 1. (a) X-ray of hands and forearms. (b) X-ray of feet. (c) CT images of craniofacial bones.

2. Materials and Methods 2.1. Patient 1. A thirty-one-year-old female patient was

admitted to Emergency Department when she was two and
We identified five patients with FD at our Endocrinology a half years old. Right femur fracture was diagnosed at
Department, Ege University Hospital, Turkey. We collected hospital. Recurrent fractures had occurred at left femur,
data on gender, age, symptoms, and findings at presentation. tibia, and humerus. Femur biopsy that was performed 7
We examined the radiographic images of our patients with years ago revealed the diagnosis of FD. During the follow-
FD. In addition, we gathered data about medical treatment up of the patient, deformity of facial bones evolved. Max-
and response to the treatment as relief of symptoms and as illofacial computed tomography (CT) revealed deformities
biochemical findings. Biochemically, serum alkaline phos- on sphenoid bone. Those deformities were obliterating max-
phatase (ALP), serum osteocalcin (OC), and deoxypyridi- illary sinus and reaching to the zygomatic bone. Ethmoid
noline (DPD) in urine were measured as bone turnover sinuses and mandibular bones were also involved. Ground
markers. In regard to bone, serum calcium (Ca), serum glass appearance was observed at the mandibular bones.
phosphor (P), and serum parathormone (PTH) levels were On the right side of cranium, there was narrowing at
recorded. All data were collected retrospectively. Total serum the level of pterygopalatine fossa and foramen rotundum.
ALP was measured with Roche Hitachi 797, Tokyo, and There were findings of exophthalmic appearance at right
normal reference range was 40–129 U/L. Serum OC and orbita (Figure 1(c)). Lytic expansile lesions were seen at the
DPD were measured with Immulite 2000, UK. Normal right iliac bone. Bending was observed at the right femur.
reference range for OC was 2–15 ng/mL and for DPD was Also, along the femur, lesions compatible with FD were
2.3–5.4 nmol/L. Plasma levels of intact parathyroid hormone present. Bone scintigraphy showed that there was increase
(PTH) were measured using a second-generation electro- in osteoblastic activity at maxillofacial sites, right and left
chemiluminescence immunoassay. We present characteris- humerus, right and left femur and tibia, ischium, and 2nd and
tics of our patients. 4th costae. As a result of craniofacial involvement, she had
Case Reports in Endocrinology 3

Table 1: Bone markers before and after bisphosphonate treatment.

Patient 1 (PFD) ALP (U/L) Ca (mg/dL) P (mg/dL) PTH (pg/mL) OC (ng/mL) DPD (nmol/L) Dvit (nmol/L)
Before tx 975 9.6 3.4 81 50.7 83.1 56
After 6 months of 1st pamidronate tx 612 9.3 3.4 66 100 65.6 —
After 6 months of 2nd pamidronate tx 632 9.7 2.8 55 93.7 41.7 —
After 2 years 520 9.2 NA 64.98 92.9 38.55 —
Patient 2 (MFD) ALP (U/L) Ca (mg/dL) P (mg/dL) PTH (pg/mL) OC (ng/mL) DPD (nmol/L) Dvit (nmol/L)
Before tx 54 10.5 4 20 10.8 5.45 24
After 12 months of 1st pamidronate tx 55 10 3.2 29 5.4 4.6 —
Patient 3 (MFD) ALP (U/L) Ca (mg/dL) P (mg/dL) PTH (pg/mL) OC (ng/mL) DPD (nmol) Dvit (nmol/L)
Before tx 66 9.6 4.7 31 5.56 10.97 40
After 12 months of 1st zoledronic a. tx 84 10.1 4.3 37.6 3.97 8 —
Patient 4 (MFD) ALP (U/L) Ca (mg/dL) P (mg/dL) PTH (pg/mL) OC (ng/mL) DPD (nmol/L) Dvit (nmol/L)
Before tx 111 9.6 3.2 32.7 25.6 11.43 31
After 12 months of 1st pamidronate tx 84 9.3 3.2 31.9 12.6 11.01 —
Patient 5 (PFD) ALP (U/L) Ca (mg/dL) P (mg/dL) PTH (pg/mL) OC (ng/mL) DPD (nmol/L) Dvit (nmol/L)
(MAS)
Before tx 227 10.5 3.9 54.5 15.8 8 29
After 3 months of 1st pamidronate tx 138 9.5 3.0 48 NA 5.2 —

facial deformity and bone pain, so operation was performed

by neurosurgeon. Pamidronate was given as 60 mg IV on
consecutive 3 days, a total of 180 mg. Bone turnover markers
after bisphosphonate treatment were presented at Table 1.
Bone pain subsided after medical treatment. There was no
new fracture and progression of bone lesions during follow-
up of a 7-year period.

2.2. Patient 2. A thirty-year-old male patient was admitted

to the hospital, Department of Plastic Surgery, with the
complaint of bone pain at mandible. Cranial CT showed that
changes at mandible were compatible with fibrous dysplasia
(not shown). FD was diagnosed 9 years ago. Pamidronate was
given as 180 mg intravenously. Bone turnover markers before
and after bisphosphonate treatment were shown in Table 1.
He had no operation. Bone pain decreased after medical
treatment.

2.3. Patient 3. A fifty-three-year-old female patient had the Figure 2: Cranial CT images of patient 3.
complaint of headache four years ago. When cranial CT
was performed there were lytic and sclerotic bone lesions
at the right frontal bone. Those lesions were compatible
with fibrous dysplasia (Figure 2). There was increased activity years ago. Cranial CT showed expansion and deformity
at cranium according to the bone scintigraphy. FD was pointing to FD at the sites of sphenoid bone, left maxillary
diagnosed clinically with the aid of imaging modalities. sinus, zygomatic bone, and mandibular bone (Figure 3(a)).
Operation was not performed. Only medical treatment was As a result of these changes, there was narrowing at the
recommended as zoledronic acid 5 mg intravenously. After inferior orbital fissure and pterygopalatine fossa. There was
zoledronic acid treatment, the complaints of the patient sub- no aeration at the left maxillary and sphenoid sinuses
sided. The changes in bone turnover markers with medical (Figure 3(a)). Increased activity at maxilla and mandible
treatment were shown in Table 1. was seen in bone scintigraphy pointed to FD (Figure 3(b)).
Pamidronate of 180 mg total dose was given intravenously.
2.4. Patient 4. A forty-three-year-old female patient was Bone pain was resolved after treatment and changes in bone
admitted to the hospital, Ear, Nose, and Throat Department, turnover markers were shown in Table 1. Bone lesions seen at
with the complaint of bone pain and facial deformity three CT were stable during follow-up.
4 Case Reports in Endocrinology

(a) (b)

Figure 3: Radiologic and scintigraphic images of patient 4. (a) Cranial CT image. (b) Scintigraphic image.

(a) (b)

Figure 4: Radiologic and scintigraphic images of patient 5. (a) Cranial CT image. (b) Scintigraphic image.

2.5. Patient 5. A forty-one-year-old male patient has had with acromegaly, it was thought that he had atypical presen-
diagnosis of FD for 20 years. FD was diagnosed according to tation of MAS, because he had no café-au-lait macules.
maxillary lesion seen at cranial CT. He has also had diagnosis In the literature there was a report of case series present-
of acromegaly for 20 years. Pituitary surgery could not be ing as atypical MAS [7]. McCune-Albright syndrome (MAS)
performed because of the maxillary and sphenoid sinus is a rare disease which is characterized by the three features:
lesion. There was scene of FD at the left temporal, sphenoid, fibrous dysplasia (usually polyostotic), café-au-lait macules,
maxillary, and mandibular bones causing expansion and and endocrine hyperfunction [7]. Endocrinopathies often
changes in density. There was a contraction of superior include sexual precocity, hyperthyroidism, hypercortisolism,
and inferior orbital fissures (Figure 4(a)). As treatment of GH excess, and hyperprolactinemia. One or two classical
acromegaly, he was using octreotide and dopamine agonist. symptoms of MAS were present in atypical MAS. GNAS
Radiotherapy for the acromegaly was performed 3 years mutation analysis was present in <50% of patients with classic
ago. Bone scintigraphy showed increased activity at left triad of MAS. Therefore, the use of mutation analysis in those
maxilla and mandible, sternum, and 1st, 5th, and 6th costae patients is limited and diagnosis of atypical MAS remains
(Figure 4(b)). Changes in bone turnover markers after 180 mg challenging [7]. In our patient GNAS mutation was not
pamidronate treatment were presented in Table 1. Together detected.
Case Reports in Endocrinology 5

Table 2: Characteristics of our patients with FD.

Age, gender Type Clinical findings at Medical department first Biopsy verified
the time of dx place of admission
P1 31 y, F Polyostotic Femur fracture Emergency Yes
P2 30 y, M Monostotic Bone pain Plastic Surgery No
P3 53 y, F Monostotic Headache Neurosurgery No
P4 43 y, F Monostotic Bone deformity ENT∗ No
P5 43 y, M Polyostotic Bone deformity Plastic Surgery Yes
∗
ENT: ear, nose, and throat.

3. Results radiologic appearance and in bone turnover markers after

medical treatment [9]. Besides, there was relief in bone pain
We identified a total of 5 patients (𝑛 = 3 F; 𝑛 = 2 M). with the pamidronate treatment given as 180 mg (60 mg/day,
Mean age of our patients was 39.6 (30–53 years) years old. consecutive 3 days) intravenously every 6 months [9]. It was
The clinical characteristics of our patients were shown in seen that the major effect of bisphosphonate treatment was
Table 2. FD was diagnosed histopathologically in our two the decrease in bone pain. In our cases, all patients had relief
patients (P1 and P5). It was diagnosed radiologically in in their bone pain. In the study of Parisi and colleague, seven
other three patients (P2, P3, and P4). We had two cases patients were given pamidronate for a mean of 6.9 years (3.7–
with polyostotic fibrous dysplasia (PFD) and 3 cases with 10.9 years) [10]. There was a significant decrease in serum
monostotic fibrous dysplasia (MFD) (Table 1). One of PFD levels of ALP and bone pain. CTX-1 levels decreased by
patients had atypical presentation of MAS (P5). This patient 56% compared to the beginning of treatment. In our cases,
had craniofacial involvement including temporal, maxillary, the longest follow-up period was 24 months with patient 1.
mandible, and sphenoid bones and costa involvement. The For other patients, mean follow-up period was 12 months.
diagnosis of FD was verified by maxillary biopsy. The other During this period, while there was a decrease in bone pain,
PFD patient (P1) had also craniofacial deformities. She there was no improvement in radiologic appearance. As far
had a craniofacial reconstructive operation for the relief of as bone turnover markers were concerned, DPD levels were
neurologic compression. decreased with treatment of pamidronate and zoledronic
Bisphosphonate treatment was preferred for five cases due acid. Because of the small number of our cases, we cannot
to bone pain and compression. Three doses of pamidronate compare the effectiveness of two different bisphosphonate
60 mg IV (total dose 180 mg) were given to four cases, treatments.
and zoledronic acid 5 mg IV was administered to one case There were no serious side effects in our patients taking
(Table 1). P1 was given 180 mg pamidronate for two times. pamidronate and zoledronic acid. In the literature, zoledronic
As far as bone turnover markers are concerned, DPD levels acid (4 mg every 6 months) was given to 9 patients after
were decreased by 54.2%, 15.5%, 3.5%, and 35.0% in P1, pamidronate in case of relapse or no response. While there
P2, P4, and P5, respectively, with treatment of pamidronate. was 60% decrease in pain, serum CTX levels decreased
Meanwhile, 26.6% decrement in DPD levels was observed by 24% with the treatment of zoledronic acid [8]. In this
in P3 with treatment of zoledronic acid (Figure 5). All our study, there was an acute phase reaction as a side effect in
patients were given calcium and vitamin D replacement to two patients [8]. It could not be possible to compare two
prevent secondary hyperparathyroidism. The complaints of bisphosphonates treatments because of the short follow-up
pain were less with bisphosphonates treatment; however, no period and lack of randomized studies. There is a need for
radiological change was observed. The bone markers of the long term studies to gather enough data about the usage of
patients before and after medical treatment were presented zoledronic acid in FD.
in Table 2. To the best of our knowledge, there was only one
randomized clinical study regarding the treatment of FD in
4. Discussion the literature. This study was a 2-year randomized, double-
blinded, placebo controlled study of oral alendronate in
FD is a rare benign bone disease. As it can be asymptomatic, FD. Alendronate was given as 40 mg/day for the patients
FD can also cause bone pain, deformity, and compression >50 kg, 20 mg for 30–50 kg, and 10 mg for 20–30 kg over a
symptoms. When fibrous dysplasia is symptomatic, medical 24-month period in 6-month cycles. Forty FD patients (24
and/or surgical treatment could be an option for therapeutic adults and 16 children) were enrolled in the study. There
modalities. All our patients were symptomatic and bisphos- was a significant decline in the bone resorption marker
phonates as medical treatment were prescribed for all our FD NTX-telopeptides in the alendronate group as compared
patients. to the placebo group at 18 months. There were no effects
Potent antiresorptive agents, bisphosphonates, were first on the bone formation marker osteocalcin and bone pain.
used in 1990s [8]. In the study of Liens et al. in 1994, It is unknown whether decrease in bone turnover markers
it was observed that there was a rapid improvement in reflects the decline in metabolic activity of FD lesions [11].
6 Case Reports in Endocrinology

Patient 1 Patient 2
90 14
13
80
12
70
11
60 10
9
50
8
40
7
30 6
5
20
4
10
3
0 2
Before tx After 6 After 6 After 2 Before tx After 12
months months years months
of 1st tx of 2nd tx of 1st tx
DPD (nmol/L) DPD (nmol/L)

Patient 3
14 Patient 4
14
13
13
12
12
11
10 11

9 10

8 9

7 8

6 7

5 6

4 5

3 4

2 3
Before tx After 12 2
months Before tx After 12
of 1st tx months of tx
DPD (nmol/L) DPD (nmol/L)

Patient 5
14
13
12
11
10
9
8
7
6
5
4
3
2
Before tx After 3 months
of tx
DPD (nmol/L)

Figure 5: The changes in urinary DPD levels before and after bisphosphonate treatment.
Case Reports in Endocrinology 7

The association between decrease in bone turnover markers References

and activity of the disease is not as clear as in the Paget disease.
Decrement in bone turnover markers may be due to effect [1] A. Shenker, L. S. Weinstein, D. E. Sweet, and A. M. Spiegel,
“An activating Gs𝛼 mutation is present in fibrous dysplasia of
of bisphosphonates on the unaffected bone. Future studies
bone in the McCune-Albright syndrome,” Journal of Clinical
including bone histomorphometry would allow more direct Endocrinology and Metabolism, vol. 79, no. 3, pp. 750–755, 1994.
investigation of the effects of bisphosphonates on FD lesions
[2] R. D. Chapurlat and P. Orcel, “Fibrous dysplasia of bone and
versus unaffected bone. Bone turnover markers may not fit
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picture is provided. Overtreatment with bisphosphonates
[3] L. Lichtenstein, “Polyostotic fibrous dysplasia,” Archives of
should be avoided. Surgery, vol. 36, no. 5, pp. 874–898, 1938.
In a case series of 26 patients with FD, 23 patients (89%)
[4] M. J. Kransdorf, R. P. Moser, and F. W. Gilkey, “Fibrous
received treatment with bisphosphonates for a median 4 years dysplasia,” Radiographics, vol. 10, pp. 519–537, 1990.
(3–276 months) [6]. Different types of bisphosphonates were
[5] L. Feller, N. H. Wood, R. A. Khammissa, J. Lemmer, and E. J.
prescribed. At the end of follow-up, most patients were on Raubenheimer, “The nature of fibrous dysplasia,” Head and Face
treatment with zoledronic acid. Three patients reported pain Medicine, vol. 5, article 22, 2009.
relief with bisphosphonate treatment. Radiologic regression [6] M. D. Thomsen and L. Rejnmark, “Clinical and radiological
was observed in 2 of 18 patients who were followed up radio- observations in a case series of 26 patients with fibrous dyspla-
logically with bisphosphonate treatment. In the remaining 13 sia,” Calcified Tissue International, vol. 94, no. 4, pp. 384–395,
patients, there was no change in radiological scene. There was 2014.
a progression in three patients [6]. [7] J. Xu, X. Li, C. S. Lv et al., “Treatment protocols for growth
As treatment option, surgery is indicated for the correc- hormonesecreting pituitary adenomas combined with craniofa-
tion of deformities, management of fractures, and relieving cial fibrous dysplasia: a case report of atypical McCune-Albright
the symptoms of compression [12]. One of our patients, syndrome,” Experimental and Therapeutic Medicine, vol. 8, pp.
P1, had surgery for recurrent femur fractures and craniofa- 877–880, 2014.
cial reconstructive surgery. Involvement of craniofacial site [8] R. D. Chapurlat, “Medical therapy in adults with fibrous
occurs in 25% of FD patients. Facial involvement can cause dysplasia of bone,” Journal of Bone and Mineral Research, vol.
both facial asymmetry and compression for the anatomic 21, no. 2, pp. 114–119, 2006.
structures located near to the affected bone [12]. Fractures are [9] D. Liens, P. D. Delmas, and P. J. Meunier, “Long-term effects
seen infrequently after puberty. In our P1, she had three times of intravenous pamidronate in fibrous dysplasia of bone,” The
fractures till adulthood and there were no fractures after that. Lancet, vol. 343, no. 8903, pp. 953–954, 1994.
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[11] A. M. Boyce, M. H. Kelly, B. A. Brillante et al., “A randomized,
Bisphosphonates may alleviate bone pain in fibrous dysplasia; double blind, placebo-controlled trial of alendronate treatment
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change in radiological findings although there was reduction [12] B. Hanifi, K. S. Samil, C. Yasar, C. Cengiz, A. Ercan, and D.
in bone turnover markers and symptoms. We recommend Ramazan, “Craniofacial fibrous dysplasia,” Clinical Imaging, vol.
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patients should be followed closely with radiological and
laboratory data for long term complications and continuity
of the treatment. Whether or not bisphosphonate slows the
disease progression needs to be determined in controlled
clinical trials.

Disclosure
This study was presented in 36th Turkey Endocrinology and
Metabolism Diseases Congress as a poster on May 21–25,
2014.

Conflict of Interests
The authors declare that they have no conflict of interests.
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