TY - THES
T1 - Microarchitectural alterations in arthritic subchondral bone
AU - Li, Guangyi
PY - 2015
Y1 - 2015
N2 - Subchondral bone, consisting of subchondral bone plate (SBP) and underlying
subchondral trabecular bone (STB), plays a pivotal role in the biomechanical and
biochemical homeostasis of the joint. Subchondral bone is widely reported to contribute
to the pathogenesis of various joint diseases.
Osteoarthritis (OA) is the most prevalent joint disease, and the leading cause of pain and
functional disability in the elderly population. Although OA has long been thought as a
primary disorder of cartilage, subchondral bone is also actively involved in the initiation
and progression of OA.
In this thesis, a general review on subchondral bone was provided. This review
summarized basic features of subchondral bone. Main risk factors influencing
subchondral bone integrity were described. Moreover, we focused on the abnormal
changes of subchondral bone in OA, and provided an overview of their potential
contribution to OA pathogenesis.
In normal joints, depth variation in the trabecular microarchitecture has been reported.
However, depth variation in osteoarthritic joint is poorly investigated. In the current
study, we observed a significant difference between the superior STB and deeper
trabecular bone (DTB) in OA. Compared to DTB, STB showed more sclerotic
microarchitecture, more active bone remodelling and higher frequency of bone cysts.
This may be due to the distinct biomechanical and biochemical functions between these
two structures.
Age and gender have remarkable impacts on bone homeostasis. However, the influence
of age and gender on bone metabolism in OA has been reported to be different from that
in normal subjects. Consequently, we investigated age and gender dependency of
microarchitecture and bone remodeling in both STB and DTB from the weight-bearing region of osteoarthritic femoral heads from 110 patients. There was no gender
difference for microarchitecture and bone remodelling in STB, while distinct gender
difference was detected in DTB. In both STB and DTB, no correlation between
microarchitecture and age was found in both genders. However, bone remodeling of
STB increased significantly with age in males, while bone remodeling parameters of
DTB increased significantly with age in females. No age or gender preference was
found in subchondral bone cysts (SBCs) frequency. The cyst volume fraction was
correlated with neither age nor gender. To conclude, OA changed the normal age- and
gender-dependence of bone homeostasis in joints, in a site-specific manner.
SBP provides structural support and significant mechanical function by transmitting
loads from cartilage towards STB. SBP is also infiltrated by a number of tiny channels,
acting as a portal for biochemical interactions between cartilage and STB. Based on the
abnormal alterations in STB observed in the previous study, we undertook a further
investigation for the relationship between SBP integrity and the homeostasis of
underlying STB in OA. Our study showed that, STB with full-thickness breach of SBP
exhibited more sclerotic microarchitecture, higher bone remodeling level and higher
SBCs frequency, as compared to those with partial-thickness breach of SBP. A mixed
pathology was detected within SBCs, including fibrous tissue, abnormal blood vessels,
fibrocartilaginous tissue, hyaline cartilaginous tissue, remnant bone fragments and
adipose tissue. Our data indicated that SBP integrity is closely associated with the
homeostasis of underlying STB in the progression of OA. SBP may act as a
biomechanical and biochemical shield between the synovial space and STB.
In contrast to the wealth of studies concerning subchondral bone in primary OA, the
alterations of subchondral bone in secondary OA remain poorly acknowledged. To
investigate subchondral bone alterations in the subset of secondary OA with
homogenous biomechanics aetiology, we collected subchondral bone specimens in
femoral heads from patients with OA secondary to hip dysplasia (HD-OA). In the
current study, the weight-bearing subchondral bone showed more sclerotic microarchitecture and more active bone remodeling in HD-OA, compared to
osteoporosis (OP). In the non-weight-bearing region, the two diseases shared similar
microarchitecture characteristics, but more active bone remodeling was detected in
HD-OA. Distinct regional difference was only observed in HD-OA. In addition,
HD-OA demonstrated more serious pathological alterations, including subchondral
bone cyst, metaplastic cartilaginous tissue, bone marrow edema and fibrous tissue,
especially in the weight-bearing region. Collectively, osteoarthritic deteriorations of
subchondral bone induced by hip dysplasia spread throughout the whole joint, but
exhibit region-dependent variations, with the weight-bearing region more seriously
affected. Biomechanical stress might exert a pivotal impact on subchondral bone
homeostasis.
Rheumatoid arthritis (RA) is a common chronic inflammatory joint disorder
characterized by persistent synovitis and juxta-articular bone erosion. However,
subchondral bone, which lies distant from the cartilage-pannus junction, is an often
neglected anatomic compartment in RA pathogenesis. Our data demonstrated that RA
and OA showed similar microarchitecture patterns in both STB and DTB, despite STB
in RA exhibiting higher bone resorption. In addition, there was no difference in SBCs
frequency between RA and OA. This may indicate that biomechanics exerts the
dominant influence on the subchondral bone microarchitecture and remodeling in the
load-bearing region which is far from the synovium, in both RA and OA.
In summary, the studies in this thesis suggested that subchondral bone was substantially
involved in the pathogenesis of OA and RA, with abnormal microarchitecture, bone
remodelling and histopathological alterations. Maintenance of subchondral bone
homeostasis may represent a potential alternative therapeutic approach for the
prophylaxis and treatment of OA and RA in the future.
AB - Subchondral bone, consisting of subchondral bone plate (SBP) and underlying
subchondral trabecular bone (STB), plays a pivotal role in the biomechanical and
biochemical homeostasis of the joint. Subchondral bone is widely reported to contribute
to the pathogenesis of various joint diseases.
Osteoarthritis (OA) is the most prevalent joint disease, and the leading cause of pain and
functional disability in the elderly population. Although OA has long been thought as a
primary disorder of cartilage, subchondral bone is also actively involved in the initiation
and progression of OA.
In this thesis, a general review on subchondral bone was provided. This review
summarized basic features of subchondral bone. Main risk factors influencing
subchondral bone integrity were described. Moreover, we focused on the abnormal
changes of subchondral bone in OA, and provided an overview of their potential
contribution to OA pathogenesis.
In normal joints, depth variation in the trabecular microarchitecture has been reported.
However, depth variation in osteoarthritic joint is poorly investigated. In the current
study, we observed a significant difference between the superior STB and deeper
trabecular bone (DTB) in OA. Compared to DTB, STB showed more sclerotic
microarchitecture, more active bone remodelling and higher frequency of bone cysts.
This may be due to the distinct biomechanical and biochemical functions between these
two structures.
Age and gender have remarkable impacts on bone homeostasis. However, the influence
of age and gender on bone metabolism in OA has been reported to be different from that
in normal subjects. Consequently, we investigated age and gender dependency of
microarchitecture and bone remodeling in both STB and DTB from the weight-bearing region of osteoarthritic femoral heads from 110 patients. There was no gender
difference for microarchitecture and bone remodelling in STB, while distinct gender
difference was detected in DTB. In both STB and DTB, no correlation between
microarchitecture and age was found in both genders. However, bone remodeling of
STB increased significantly with age in males, while bone remodeling parameters of
DTB increased significantly with age in females. No age or gender preference was
found in subchondral bone cysts (SBCs) frequency. The cyst volume fraction was
correlated with neither age nor gender. To conclude, OA changed the normal age- and
gender-dependence of bone homeostasis in joints, in a site-specific manner.
SBP provides structural support and significant mechanical function by transmitting
loads from cartilage towards STB. SBP is also infiltrated by a number of tiny channels,
acting as a portal for biochemical interactions between cartilage and STB. Based on the
abnormal alterations in STB observed in the previous study, we undertook a further
investigation for the relationship between SBP integrity and the homeostasis of
underlying STB in OA. Our study showed that, STB with full-thickness breach of SBP
exhibited more sclerotic microarchitecture, higher bone remodeling level and higher
SBCs frequency, as compared to those with partial-thickness breach of SBP. A mixed
pathology was detected within SBCs, including fibrous tissue, abnormal blood vessels,
fibrocartilaginous tissue, hyaline cartilaginous tissue, remnant bone fragments and
adipose tissue. Our data indicated that SBP integrity is closely associated with the
homeostasis of underlying STB in the progression of OA. SBP may act as a
biomechanical and biochemical shield between the synovial space and STB.
In contrast to the wealth of studies concerning subchondral bone in primary OA, the
alterations of subchondral bone in secondary OA remain poorly acknowledged. To
investigate subchondral bone alterations in the subset of secondary OA with
homogenous biomechanics aetiology, we collected subchondral bone specimens in
femoral heads from patients with OA secondary to hip dysplasia (HD-OA). In the
current study, the weight-bearing subchondral bone showed more sclerotic microarchitecture and more active bone remodeling in HD-OA, compared to
osteoporosis (OP). In the non-weight-bearing region, the two diseases shared similar
microarchitecture characteristics, but more active bone remodeling was detected in
HD-OA. Distinct regional difference was only observed in HD-OA. In addition,
HD-OA demonstrated more serious pathological alterations, including subchondral
bone cyst, metaplastic cartilaginous tissue, bone marrow edema and fibrous tissue,
especially in the weight-bearing region. Collectively, osteoarthritic deteriorations of
subchondral bone induced by hip dysplasia spread throughout the whole joint, but
exhibit region-dependent variations, with the weight-bearing region more seriously
affected. Biomechanical stress might exert a pivotal impact on subchondral bone
homeostasis.
Rheumatoid arthritis (RA) is a common chronic inflammatory joint disorder
characterized by persistent synovitis and juxta-articular bone erosion. However,
subchondral bone, which lies distant from the cartilage-pannus junction, is an often
neglected anatomic compartment in RA pathogenesis. Our data demonstrated that RA
and OA showed similar microarchitecture patterns in both STB and DTB, despite STB
in RA exhibiting higher bone resorption. In addition, there was no difference in SBCs
frequency between RA and OA. This may indicate that biomechanics exerts the
dominant influence on the subchondral bone microarchitecture and remodeling in the
load-bearing region which is far from the synovium, in both RA and OA.
In summary, the studies in this thesis suggested that subchondral bone was substantially
involved in the pathogenesis of OA and RA, with abnormal microarchitecture, bone
remodelling and histopathological alterations. Maintenance of subchondral bone
homeostasis may represent a potential alternative therapeutic approach for the
prophylaxis and treatment of OA and RA in the future.
KW - Osteoarthritis
KW - Hip dysplasia
KW - Rheumatoid arthritis
KW - Subchondral bone plate
KW - Subchondral trabecular bone
KW - Cyst
KW - Microarchitecture
KW - Bone remodeling
M3 - Doctoral Thesis
ER -