Ir J Med Sci
DOI 10.1007/s11845-014-1199-8
REVIEW ARTICLE
Ceramic and non-ceramic hydroxyapatite as a bone graft
material: a brief review
S. R. Dutta • D. Passi • P. Singh • A. Bhuibhar
Received: 4 May 2014 / Accepted: 2 September 2014
Ó Royal Academy of Medicine in Ireland 2014
Abstract Treatment of dental, craniofacial and orthope-
dic defects with bone graft substitutes has shown promising
result achieving almost complete bone regeneration
depending on product resorption similar to human bone’s
physicochemical and crystallographic characteristics.
Among these, non-ceramic and ceramic hydroxyapatite
being the main inorganic salt of bone is the most studied
calcium phosphate material in clinical practices ever since
1970s and non-ceramic since 1985. Its ‘‘chemical similar-
ity’’ with the mineralized phase of biologic bone makes it
unique. Hydroxyapatite as an excellent carrier of osteoin-
ductive growth factors and osteogenic cell populations is
also useful as drug delivery vehicle regardless of its den-
sity. Porous ceramic and non-ceramic hydroxyapatite is
osteoconductive, biocompatible and very inert. The need
for bone graft material keeps on increasing with increased
age of the population and the increased conditions of
trauma. Recent advances in genetic engineering and doping
techniques have made it possible to use non-ceramic
S. R. Dutta (&)
Department of Oral and Maxillofacial Surgery, M. B. Kedia
Dental College, Tribhuvan University, Chhapkaiya, Birgunj,
Nepal
e-mail: drshubharanjand@gmail.com
D. Passi
Department of Oral and Maxillofacial Surgery, E. S. I. C., Dental
College and Hospital, Rohini, Delhi, India
P. Singh
Department of Physiology, Vyas Dental College and Hospital,
Jodhpur, Rajasthan, India
A. Bhuibhar
Department of Oral and Maxillofacial surgery, Vyas Dental
College and Hospital, Jodhpur, Rajasthan, India
hydroxyapatite in larger non-ceramic crystals and cluster
forms as a successful bone graft substitute to treat various
types of bone defects. In this paper we have mentioned
some recently studied properties of hydroxyapatite and its
various uses through a brief review of the literatures
available to date.
Keywords Bone graft substitute
Ceramic
hydroxyapatite
Coralline ceramic hydroxyapatite

Bioactive non-ceramic hydroxylapatite
Osteoconductive

Biocompatible
Introduction
The extensive acceptance of bone graft materials for
orthopedic surgeries involving articular and osseous
defects in multitudinous reconstructive procedures depends
on its vast availability and immense usefulness [1]. In the
past few years the use of bone graft substitutes in the
treatment of distal radius fractures has also increased [2–6].
Bone graft materials promote osseous ingrowth and bone
healing by providing a non loading structural substrate.
Bone grafting provides structural support or augments
healing in significant bone defects such as osteoporotic
bone and non-union fracture. The bone graft substitutes are
based on naturally occurring materials such as demineral-
ized allograft bone matrix, bovine collagen mineral com-
posites, ceramic hydroxyapatite (HA), non-ceramic
hydroxylapatite, ceramic-coralline hydroxyapatite (CHA)
and synthetic materials such as calcium sulfate pellets, and
non-ceramic calcium phosphate pellets bioactive glass, and
calcium phosphate cement. Extensive studies in animal
model and human patient has been done to evaluate the
possible advantages of using bone graft material.
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Fig. 1 Structure of HA
Bone graft substitutes
Among the several materials starting from gold to allograft
used to repair bone defects [7, 8] autologous bone is still
considered as the gold standard [9]. However, the use of
autologous bone is limited because of high cost. Also it
requires a second surgical site resulting in additional pain
and complications, and is associated with significant donor
site morbidity. The rapid resorption of allograft bone used
in the form of fresh-frozen or demineralized freeze dried
bone allograft can make it less ideal for some larger
defects. Recently xenograft materials have also been used
successfully as bone graft substitutes [7, 10–13]. Ceramic
Bovine bone derivative is also used as a bone substitute as
it mimics the natural architecture of the cancellous bone
even after undergoing heat treatment and chemical
extraction process [14]. A number of synthetic bone graft
substitutes also have been developed for the repair of bony
defects, especially in the craniofacial area. Most of these
are based on HA or other calcium phosphate minerals,
similar to the natural mineral found in human bone. Cal-
cium salts, mainly HA, help in bridging large segmental
defects by the process of osteoconduction, thus getting
deposited on the collagenous framework of the bone by the
osteoblasts [15]. Studies have shown chemical and crys-
tallographic similarity of synthetic HA to the naturally
occurring HA [16–19]. Hence, these materials are osteo-
conductive, biocompatible and can be easily sterilized and
used in the clinic.
Hydroxyapatite
Hydroxyapatite as the main inorganic salt of bone and
teeth, is the most studied calcium phosphate material in
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Ir J Med Sci
Fig. 2 HA used in alveolar defects
Fig. 3 HA used in augmentation genioplasty
clinical practices ever since 1970s [20]. Hydroxyapatite is
calcium phosphate bioceramic and is also referred to as
ceramic hydroxylapatite used as a bone defect filler,
hydroxylapatite. It is generally recognized as the natural
biologic mineral component of vertebrate hard tissue and is
comprised in 60–70 % bone in the formula of [Ca5(-
PO4)3OH] and 98 % dental enamel (Fig. 1).
The composition of HA ceramic is [Ca10(PO4)6OH2]
with a idealized Ca/P ratio 1.67, is not found in human
biologic hydroxylapatite. The existence of a direct chemi-
cal bond between bone and ceramic and non-ceramic bio-
active hydroxylapatite (OsteoGenÒ [Ca5(PO4)3(OH)]) has
been reported [21]. Filling defect site with bioactive
hydroxylapatite, new bone formation was evident by 95 %,
in a critical side defect of 8 mm 9 1 mm wide (Valen
Ricci Spivak) by histological studies of bone–hydroxyl-
apatite interaction [21] through the combination of extra-
cellular matrix components and direct physicochemical
deposition on ceramic OsteoGenÒ, however, demonstrated
sparingly 8 % new bone deposition touching the ceramic
HA surface coating intermittently (Ricci, Spivak) at the
tissue–titanium implant interface. Ceramic HA is generally
Ir J Med Sci
Fig. 4 HA used to increasing the height of alveolar ridge
Fig. 5 HA used for reconstruction of resected mandible
produced by a hydrothermal exchange reaction of the
natural reef building coral skeleton in which the calcium
carbonate skeleton is converted to calcium phosphate
without changing the trabecular bone imitating structure of
the coral [22]. The uniqueness of this material is its
chemical similarity with the mineralized phase of bone
which accounts for the osteoconductive potential and
excellent biocompatibility [23–25].
The clinical use of ceramic HA mainly in granular form
has been reported in dental, craniofacial as well as in
orthopedic surgery (Figs. 2, 3, 4, 5) [26–30].
HA is osteophilic, osteoconductive and osteointegrated.
It can get bonded to the bone directly through the natural
bone converting mechanism [31]. The calcium HA/tri-
calcium phosphate (60/40) provides a structure or scaffold
in close interface with adjacent bone. Thus, its use in the
treatment of load-bearing segmental bone defects is con-
fined only to a limited number of cases, but without any
failure reports at the early stages of implantation [32]. Tri-
calcium phosphate can undergo partial conversion to HA
once it is implanted into the body and this characteristic
makes it a random porous ceramic. As tri-calcium phos-
phate is highly porous and quickly resorbed into bone it
becomes mechanically weak in compression after conver-
sion whereas HA is resorbed slowly and large segments of
it can remain in place for years. The unpredictable bio-
degradation profile of tri-calcium phosphate has made it an
unpopular bone graft substitute [33]. However, bone
defects as an outcome of trauma, benign tumors, and uni-
cameral cysts can be effectively filled by tri-calcium
phosphate [34] or by non-ceramic bioactive hydroxylapa-
tite. (Spivak, Ricci, Valen) (Valen Letter to the Editor—
enclosed) (Kimoto Part 1) (Nordquist Part II-Part III) [21,
35–40]. The benefits of non-ceramic bioactive hydroxyl-
apatite in dentistry have been demonstrated especially for
the surface conversion to fluorapatite for bacteriostatic
control and mitigation or elimination of pathogens and for
cell differentiation and proliferation of human osteoblast
(Ohno) [41]. Fluoridated hydroxyapatite (fluorapatite),
shows promise as an adjunctive treatment component in
inhibiting peri-implant infection [40]. HA is an excellent
carrier of osteoinductive growth factors and osteogenic cell
populations and hence also useful as a bioactive delivery
vehicle [42]. Radiographic evidences are available sug-
gesting that carbonated HA used in distal radius corrective
osteotomies have 100 % union rate of graft integration into
the bone tissue. There was also improvement in range of
wrist motion, forearm rotation as well as grip strength [6].
Thus, these studies confirmed the use of HA as an excellent
bone graft substitute in orthopedic surgeries as it facilitates
bone formation, is biocompatible and slow remodeling
material.
The origin of HA ceramic may be natural or artificial
(synthetic). Synthetic ceramic HA acts as a framework for
the ingrowth and helps in subsequent deposition of new
bone [43]. In recent years the technique of doping of bi-
oceramic materials are also adopted to enhance their
mechanical and biological properties as well as cytocom-
patibility for use in tissue engineering applications [44, 45].
Synthetic HA are also used as a coating material for dental
and orthopedic implants, but its moderate to low solubility
within the body and mechanical properties that differ from
surrounding tissue and bone [44] limits its use. The use of
doped HA with manganese and/or zinc as a bone substitute
has resulted in faster resorption kinetics [46]. The use of
plasma spray HA coating as a means of fixation on metallic
femoral stem and cup has also been reported [47]. HA-
coated pins enhance pin fixation irrespective of bone type
and loading conditions. This reduces the rate of infection
and loosening during external fixation [48, 49].
Porous hydroxyapatite
Synthetic porous HA bone graft materials are osteocon-
ductive, biocompatible and slowly resorbing bone
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substitute. The use of porous HA has replaced the use of
dense form of HA due to its better integration to bone by
direct bonding to the bone. This facilitates osteoblastic
proliferation into the micropores and acts as a scaffold for
bone regeneration [50–52]. Studies have shown that treat-
ment of bony defects by HA leads to bone growth into
18–74 % pores of new bone area as compared to total
implant area [53, 54]. However, probably the entire porous
space of the implant is never completely filled with bone
[55]. Porous HA can be produced either by homogenizing
calcium phosphate powder with naphthalene particles or by
the decomposition of hydrogen peroxide to generate a
pore-filled structure. The interconnected high porous
structure of HA has been promising for postero-lateral
lumbar inter-transverse process spine fusion [56, 57].
Several studies have shown that porous HA is osteocon-
ductive, biocompatible and very inert [58, 59]. It resorbs
with time but the degradation rate is very slow [60].
However, porous HA is brittle and can be used only in non-
loading sites and will act as a high stress riser, compro-
mising the host bone with fibrous tissue encapsulation and
fracture points under load. Its compressive strength is
enhanced by bone ingrowth, comparable only to that of
cancellous bone [53].
Coralline hydroxyapatite
Coralline hydroxyapatite (CHA) is also an alternative to
bone graft. The pore structure and biomechanical proper-
ties of CHA is similar to human cancellous bone. It is
equally efficient to autogenous cancellous bone in the use
for subchondral support during internal fixation of tibial
plateau fractures. It provides the structural integrity to
support an articular surface and also osteoconductive
matrix for bony ingrowth [60]. CHA is processed by a
hydrothermal exchange method in which the coral calcium
phosphate is converted to crystalline HA with pore diam-
eters between 200 and 500 lm, and a structure resembling
human trabecular bone. Cases of articular surface depres-
sion in tibial plateau fractures have reported that the clin-
ical performances of autologous cancellous bone graft and
CHA are equivalent when used for filling bone voids [61].
The use of CHA has been successful in non-weight-bearing
applications such as maxillofacial, periodontal augmenta-
tion [62] and distal radial fractures [60] as well as in
weight-bearing metaphyseal defects (i.e. tibial plateau
fractures) [63]. However, initially it needs support by
internal fixation until completion of fibro-osseous ingrowth
because of mechanical weakness. Bone graft expansion in
spinal fusions [64, 65] and orbital restorations [66] are
other clinical uses of CHA. A clinical study in 1999
reported that 19 distal radius fractures were treated using
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Ir J Med Sci
internal and external fixation implanted CHA bone graft as
a substitute for autogenous bone graft to support the
reduced articular surface of 21 consecutive patients with
distal radius fractures treated with external fixation and
K-wire [60]. This single-cohort retrospective study was
undertaken to report the outcomes of treatment with this
material, associated contraindications, and its efficiency in
articular surface reduction. After 35 months of surgery 18
patients were available for analytical procedures involving
radiography, subjective outcome analysis and independent
evaluation of motion. 17 patients had good or excellent
radiographic results. The use of CHA in combination with
external fixation and K-wires was effective at maintaining
articular surface reduction and its safety profile was com-
parable to other forms of the treatment.
The need for bone graft material keeps on increasing
with increased age of the population and the increased
conditions of high velocity trauma. Autografts remain the
gold standard because they contain the requisite osteoin-
ductive, osteogenic and osteoconductive properties neces-
sary to regenerate bone. There are drawbacks to harvesting
autograft, including increased operating time, potential
complications and morbidity of the harvest site and limi-
tations in available bone quantity. Due to these limitations
there has been significant effort placed on the development
of various categories of bone graft substitutes, including
calcium phosphate and hydroxyapatite materials. We can
conclude from the study of literatures described above that
in the near future these bone graft substitutes such as
hydroxyapatite can form a new approach or idea of treat-
ment in the patients with bony defects, especially in elderly
people with unstable, extra-articular and comminuted distal
radius fractures, thus preventing secondary collapse, pro-
viding better post-operative rehabilitation and improving
functional outcome. The modern day research on available
bone graft substitutes involving the methods of genetic
engineering and refinements in internal fixation techniques
might be, therefore, helpful in managing bone defects,
including periodontal defects such as intrabony defect and
maxillofacial defects such as reconstruction of excision of
primary bone tumor, craniofacial defects such as cleido-
cranial dysplasia as well as for treating orthopedic defects
such as distal radius fractures.
Conflict of interest None.
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