University of Applied Sciences Ansbach

International Product and Service Management

Report on

Calcium Phosphate Cements for Vertebroplasty

Course: Biomaterials in Medicine

Tutor: Prof.Dr. Andreas Boger

Student: Mahak Ajmera (85371)

Submitted on: 13.12.2013

Table of Contents

1. Abstract .................................................................................................................................. 1
2. Introduction ........................................................................................................................... 1
3. Methods ................................................................................................................................. 2
4. Results and Discussion ........................................................................................................... 3
4.1 Calcium Phosphate cements ......................................................................................... 3
4.2 Calcium Phosphate cements products .......................................................................... 3
4.3 Clinical cases .................................................................................................................. 4
5. Conclusion .............................................................................................................................. 4
6. References ............................................................................................................................. 5
1. Abstract
One of the popular bone graft substitute, especially in spine surgery is calcium phosphate cements
(CPCs). This article presents a comparative analysis of the characteristics of different bone grafts
substitute and talks about the widespread products used in spine surgery concerning experience of
their use.

2. Introduction
The bones in the spinal column are referred as vertebrae. A vertebral fracture is caused by break in
one of these bones. A vertebral compression fracture occurs when the front part of the bone is
squeezed or compressed (figure 1) due to osteoporosis, low bone mineral density, advanced age,
cancer, tumor, trauma and degenerative spine conditions [1]. The symptoms can be mild to severe
pain in the middle or lower back, numbness, tingling or weakness, difficulty in walking and loss of
control of the bowel or bladder.

Figure 1: Vertebral Compression Fracture [2]

The method used to cure this is by injecting the bone cement into the vertebrae (figure 2). It
relieves pain associated with vertebral compression fractures [3]. The ideal cements used for
vertebroplasty should be biocompatible, easy and safely injectable, possess sufficient radio opacity,
have adjusted setting time and adaptable mechanical properties.

Figure 2: Injection of bone cement into vertebrae [4]

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3. Method
Polymethylmethacrylates (PMMAs), composite cements and CPCs are the three bone cements which
can be used in vertebroplasty. The characteristics of these cements are summarized in table 1.

PMMAs are the most widely used and were the first cements available for vertebroplasty. They
combine the advantage of long trial experience, low cost, good radio-opacity with some drawbacks
of bad osteo integration, high polymerization temperature and non-bioactivity [5].

The composite cements (Bisphenol-a-glycidyldimethacrylate resins) combine biocompatibility with

easy handling; they also overcome disadvantages of PMMA as exothermic reaction, possibility of the
release of unreacted monomer in the circulatory system and modification of the initial composition
of the PMMA. Another advantage is the low curing temperature at which they become solid and
mechanical properties however they lack good radio opacity [6].

Calcium phosphate cements (CPCs) are made of one or several calcium phosphate (CaP) powders
and an aqueous solution. The compositions of this cement make it a “bone-like” cement that avoids
the problems of toxicity inside and outside the bone (if a leakage occurs). CPCs are the most
biocompatible cements. The non-toxic and non-carcinogenic properties make them more suitable
than PMMA bone cements. Other interesting properties are non-exothermic setting and negligible
shrinkage. In addition they show calcium phosphate cements show excellent bioresorption
nevertheless, their mechanical properties are lower than those of PMMAs [6].

Table 1: Comparison of Bone cements [6]

S. No Characteristics PMMA Composite Calcium Phosphate

Cement Cement
1 Biocompatibility Non Biocompatible Biocompatible Highly
Biocompatible
2 Radio Opacity Good radio opacity Low radio opacity Good radio opacity

3 Curing temperature High Low Low

4 Toxic Yes No No

5 Cost Low High High

6 Bioresorption No No Yes

7 Mechanical Properties High High Low

Compressive strength 82Mpa 210Mpa 10-100Mpa

Tensile strength 27Mpa 57Mpa 1-10 Mpa

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4. Results and Discussion
4.1 Calcium Phosphate Cements

Calcium phosphate (CaP) compounds have triggered interest as a synthetic bone graft substitutes
since they have similarity to bone mineral composition, bioactivity, osteoconductivity and ability to
form a strong interface with bone. Blocks granules, coatings on dental and medical implants and
cements are example of different CaP biomaterials. The property of being injectable and easy to
shape helps to fill geometrically complicated bone defects. CPCs are made of combinations of CaP
powders and an aqueous solution which forms a paste. The various combinations of powders are
tetracalcium phosphate (TTCP), Hydroxylapatite (HA), dicalcium phosphate dihydrous (DCPD or
brushite), α- tricalcium phosphate (α-TCP) and β – tricalcium phosphate (β-TCP) [7].

4.2 Calcium Phosphate Cements (CPCs) Products

CPCs products approved for Vertebroplasty by FDA (Food and Drug Administration) are summarized
in Table 2[8].

Table 2:Calcium Phosphate Cements (CPCs) based products on the market

S. No Product Company Name Chemical Composition Source

Name
1 Bonesource Stryker Powder: Dicalcium phosphate dehydrate, [9]
Orthopedics, Tetracalcium phosphate
Mahwah, NJ Liquid: Phosphate Solution, Distilled Water
2 HydroSet Stryker Powder: Dicalcium phosphate dehydrate, [10]
Orthopedics, Tetracalcium phosphate, Tri-sodium citrate
Mahwah, NJ Liquid: Sodium phosphate,
Polyvinylpyrrolidone, Distilled Water
3 Beta-BSM ETEX Corporation, Powder: Amorphous calcium phosphate, [11]
Cambridge, MA Calcium phosphate Acid, Dicalcium
phosphate dehydrate
Liquid: Sodium phosphate, Water
4 Calcibon Biomet, Germany Powder: α-tricalcium phosphate dehydrate, [12]
Calcium hydrogen phosphate, Calcium
carbonate,Hydroxylapatite
Liquid:Distilled Water, Sodium hydrogen
phosphate solution
5 Biopex Mitsubishi Powder: α-tricalcium phosphate dehydrate, [13]
materials, Tokyo, Tetracalcium phosphate, Dicalcium
Japan Phosphate, Hydroxylapatite
Liquid: Distilled Water, Chondroitin sodium
sulphate, Sodium succinate

3
4.3 Clinical Cases

4.3.1 Biopex, Tokyo Japan

In this study the long term clinical and radiographic outcomes are evaluated after vertebroplasty
using CPC (Biopex) for treatment of osteoporotic vertebral fractures (OVF). About 106 patients were
reviewed for the clinical study and among those 8 died in two years and 12 lost the follow up. Two
procedures were followed, first was Vertebroplasty using CPCs in patients with osteoporotic burst
fracture (41 patients) and second was vertebroplasty using CPC in patients with osteoporotic
compression fracture (65 Patients). The result of the study was that all patients reported decreased
pain according to VAS (Visual analogue scale) immediately after vertebroplasty and pain relief was
maintained till the last follow up without new osteoporotic vertebral fractures [14].

Using Biopex CPCs gave a satisfactory outcome and no delayed complications in elderly patients with
osteoporotic vertebral fractures in follow up time of 2 years.

4.3.2 Norian XR, Cupertino, CA

Medical device maker Synthes Inc. and Norian subsidiary was charged for illegally testing Norian XR
bone cement on humans, which lead to death of five patients on the operating room table due to
rapid drop in blood pressure after the surgeon injected the cement[15].

Synthes has tested a product called Norian XR, cement that has a unique capacity to turn into bone
when injected into human skeleton. It was approved by FDA, in 2002 for use in arm but not in spine
with a prior notice, as it contains multiple blood vessels and any leakage could send cement to lungs
and heart leading to death, but the company pushed it forward anyway. A clinical trial for using
Norian XR in Vertebroplasty would take 3 years and $ 1 million. They decided not to pursue an IDE
(Investigational Device Exemption) study but to perform 60-80 procedures and publish their clinical
results.

In spring 2002, Synthes funded an animal study for Norian XR and the results were alarming. When
Norian XR was injected into the bloodstream of a pig, “the entire pulmonary artery system had
clotted off”. The surgeons had injected Norian XR into a large vein leading to the pig’s heart to
simulate what would happen if the cement leaked during vertebroplasty. The scientist noted that a
relatively small amount of Norian XR resulted in the formation of a very large volume of clot, which
blocked the flow of blood inside the heart and lungs, and the pig died in less than 30 seconds. In
October 2010, Synthes was pleaded guilty and agreed to pay $23 million fines and divest Norian
XR[15].

5. Conclusion
An optimized cement formula is the need for vertebroplasty. The disadvantages of PMMA is its high
curing temperature, toxicity and is non biocompatible. Vertebroplasty has become an important
treatment option and has great potential. The discovery of CPCs has opened up new horizons in the
use of CaP in spinal surgery. Several CPCs are now on the market. However there is a need to
improve their mechanical properties.

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6. References
[1] Old JL, Calvert M; Vertebral Compression Fractures in the Elderly. Am Fam Physician. 2004 Jan
1;69(1):111-116

[2]http://medicine.med.nyu.edu/conditions-we-treat/conditions/vertebral-compression-
fractureaccessed on 09/12/2013

[3]National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of

Osteoporosis. 2008.

[4] http://helpingbacks.com/conditions/spinal-fracture/treatment/vertebroplasty

[5] Boger, Prof.Dr.Andreas in Ansbach University of Applied Sciences (2013): Lecture notes for the
lecture Biomaterials in medicine in the winter term 2013/14 for the course International Product
and Service Management at Ansbach University of Applied Sciences. Slide (50)

[6]www.openradiology.org/zosirws/survey/vertebroplasty/cementsreview/calciumphosphate
Accessed on 10/12/2013

[7]Shahrouzi J, Hesaraki S., Zamanian A.; The Effect of Paste Concentration on Mechanical and
Setting Properties of Calcium Phosphate Bone Cements, Advanced Chemical Engineering Research
(ACER); Volume 1 Issue 1,pp 1-7, December 2012

[8]Lieberman IH, Togawa D, Kayanja MM; Vertebroplasty and Kyphoplasty: Filler Materials; The
Spine Journal 5 (2005) 305S–316S

[9]http://www.stryker.com/stellent/groups/public/documents/web_prod/023526.pdf Accessed on
09/12/2013

[10]http://www.stryker.com/en-us/products/Orthopaedics/BoneSubstitutes/Hydroset/index.htm
Accessed 09/12/2013

[11]www.orthopediatrics.com/binary/org/ORTHOPEDIATRICS/doc/ETEX%20Beta%20Sales%20Sheet
%20edit.pdf Accessed 09/12/2013

[12]http://www.biomet.com.tr/tr-medical/tr-biomaterials/tr-calcibon Accessed on 09/12/2013

[13]http://www.taisho.co.jp/en/company/release/2000/060600-e.htm Accessed on 09/12/2013

[14]Nakano et al; Vertebroplasty using calcium phosphate cements for osteoporotic vertebral
fractures: study of outcomes at a minimum follow- up of two years; Asian Spine Journal Vol.6, No.1,
pp 34-42, 2012

[15]http://features.blogs.fortune.cnn.com/2012/09/18/synthes-norian-criminal Accessed on
09/12/2013