Open Access Repository

Systemic factors, structural biomarkers and vitamin D treatment in knee osteoarthritis

Downloads

Downloads per month over past year

Jin, X (2016) Systemic factors, structural biomarkers and vitamin D treatment in knee osteoarthritis. PhD thesis, University of Tasmania.

[img]
Preview
PDF (Whole thesis (published material removed))
Jin_whole_thesi...pdf | Download (8MB)
Available under University of Tasmania Standard License.

| Preview
[img] PDF (Whole thesis)
Jin_whole_thesi...pdf | Document not available for request/download
Full text restricted
Available under University of Tasmania Standard License.

Abstract

Osteoarthritis (OA) is a multifactorial disease of the joints and is a leading cause of pain and
disability in older adults. The knee is the most common joint affected by OA. Up to the date
of this thesis, there are no approved disease-modifying treatments available for knee OA.
Therefore, there is an urgent need for identifying modifiable risk factors for this disease. This
thesis aims to use a mixed approach to investigate multiple aspects of the disease, including
the roles of systemic risk factors in knee OA, the effects of vitamin D supplementation on
disease progression, as well as the predictive values of magnetic resonance imaging (MRI)
biomarkers for knee replacement.
Chapter 4 systematically reviews 32 studies on the relationship between serum C-reactive
protein levels measured by a high sensitivity method (hs-CRP) and OA, as well as the correlation
between circulating CRP levels and OA phenotypes. Serum hs-CRP levels in OA
were modestly but statistically significantly higher than controls. The levels were significantly
associated with pain and decreased physical function, but not radiographic OA. This
suggests low-grade systemic inflammation may play a greater role in symptoms rather than
radiographic changes in OA.
Chapter 5 describes the longitudinal relationship between adiposity and change in knee pain.
Data from a population-based sample of older adults show that body mass index (BMI) is
the most consistent correlate of knee pain. Fat mass is associated with non-weight-bearing
knee pain suggesting systemic mechanisms are involved.
Chapter 6 investigates the effects of vitamin D supplementation versus placebo on knee pain and knee cartilage volume in symptomatic knee OA patients with low vitamin D levels in a
randomized clinical trial. Compared with placebo, vitamin D supplementation did not result
in significant differences in change in MRI-measured tibial cartilage volume or knee pain
score over 2 years. There were no significant differences in changes of tibiofemoral cartilage
defects or bone marrow lesions; however, fewer of those receiving vitamin D had increases
in bone marrow lesions.These findings do not support the use of vitamin D supplementation
for preventing tibial cartilage loss or improving knee pain in patients with knee OA.
Chapter 7 describes the longitudinal associations between serum levels of estrogen, progesterone
and testosterone and MRI knee structural changes in both males and females with
symptomatic knee OA. For women, progesterone was associated with cartilage volume and
estradiol levels were inversely associated with grades of bone marrow lesions (BMLs), while
estradiol, progesterone and testosterone were inversely associated with effusion-synovitis
volume. No consistent associations were observed for men. This suggests endogenous sex
hormones may be protective for joint structural changes in women but not men, which may
contribute to observed sex differences in knee OA.
Chapter 8 describes the independent association of MRI markers and total knee replacement
(TKR) over 10.7 years in older adults from a general population. MRI markers studied
included cartilage defects, BMLs, effusion-synovitis and meniscal pathologies. Cartilage
defects, BMLs and meniscal tears, but not effusion-synovitis or meniscal extrusion in the
right knee were independent predictors of TKR in either knee over 10.7 years. The presence
of multiple pathologies increased the risk of TKR, suggesting that MRI structural markers
are good predictors of rapid knee OA progression in the general population.
In conclusion, this series of studies indicate that knee OA is a complex disease that is associated
with systematic factors such as low-grade inflammation, adiposity and sex hormones.
Vitamin D supplementation does not significantly prevent knee cartilage loss and knee pain in patients with symptomatic knee OA. MRI structural markers are good predictors of endstage
knee OA in the general population. Future study should continue to validate the utility
of using a panel of MRI biomarkers in predicting clinical endpoints. When developing
disease-modifying OA drugs (DMOADS), systemic and metabolic inflammation should be
a potential treatment target. Further investigation is needed to examine the effects of exogenous
hormone replacement therapy on MRI structural changes in women.

Item Type: Thesis (PhD)
Keywords: Knee Osteoarthritis; Vitamin D; Magnetic Resonance Imaging; Chronic Inflammation; Adiposity; Sex Hormones
Copyright Information:

Copyright 2016 the Author

Additional Information:

Chapter 4 appears to be the equivalent of a post-print version of an article published as: Jin, X. et al. (2015). Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis. Annals of the rheumatic diseases, 74(4), 703-10.

Chapter 5 appears to be the equivalent of a post-print version of an article published as: Jin, X. et al. (2016). Longitudinal associations between adiposity and change in knee pain: Tasmanian older adult cohort study. Seminars in arthritis and rheumatism, 45(5) 564-569 first published online 18/10/2015

Chapter 6 appears to be the equivalent of a post-print version of an article published as: Jin, X. et al. (2016). Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis: a randomized clinical trial. JAMA 315 (10) 1005-101313.

Chapter 7 appears to be the equivalent of a pre-print version of an article published as: Jin, X. et al. (2016). Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis, l: Osteoarthritis and cartilage, 24(sup1), S358-S359

Date Deposited: 01 Nov 2016 01:04
Last Modified: 02 Dec 2016 01:09
Related URLs:
Item Statistics: View statistics for this item

Actions (login required)

Item Control Page Item Control Page
TOP