Osteoarthritis and Osteoporosis: Is There A Link?

OSTEOARTHRITIS AND
OSTEOPOROSIS:
IS THERE A LINK?
Swan Sim Yeap
Consultant Rheumatologist
Subang Jaya Medical Centre, Malaysia
Overview
• Relationships between osteoarthritis (OA) and
osteoporosis (OP)
• Clinical
• BMD
• Fracture
• Falls
• Genetic
• Vitamin D
• Use of OP drugs in OA
What is OA?
• OA is JOINT
FAILURE, caused
by abnormal
mechanical
stress/loading and
the resultant attempt
at joint repair
Dieppe P. Developments in OA.
Rheumatology 2011; 50: 245–247
Nelson AE, Jordan JM. Osteoarthritis
Cart 2012; 20: 1-3
Current Definition of Osteoporosis
Osteoporosis is defined as a skeletal disorder characterized
by compromised bone strength predisposing a person to an
increased risk of fracture. Bone strength primarily reflects the
integration of bone density and bone quality.
Normal bone
Osteoporosis
NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95
Risk Factors for OA and OP
Butlink IEM and Lems WF. Curr Rheumatol Rep 2013; 15: 328
CLINICAL LINKS BETWEEN
OA AND OP
Bone Density
Higher BMD in OA Compared to OP at the
Femur
Foss MVL and Byers PD. Ann
Rheum Dis 1972; 31: 259-64
Radiographic OA is Associated with
Higher FN BMD
Knee OA
Hip OA
Burger H et al. Arthritis Rheum 1996; 39: 81-6
FN BMD and Knee OA: Framingham
Study
Zhang Y et al. J Rheumatol 2000; 27: 1032-7
Incident Knee OA
Progression of Knee OA
Percentage (%)
16
40
14
35
12
30
10
25
8
20
6
15
4
10
2
5
0
0
Lowest Second Third Highest
Quartiles of BMD
Lowest Second Third Highest
Increased Baseline BMD in Incident Knee OA
Hip BMD
Lumbar spine BMD
Hart DJ et al. Arthritis Rheum 2002; 46: 92-9
Increased Risk of Developing ROA Knee
with Higher BMD
Patients with OA have higher BMD.
Higher BMD seems to be associated with
an increased risk of incident knee OA.
CLINICAL LINKS BETWEEN
OA AND OP
Fracture
Risk of OP Fracture by OA Status
Despite having increased BMD compared to controls,
subjects with OA did not have a significantly reduced
risk of osteoporotic fracture
Relationship Between OA and OP
Fracture
Despite having increased BMD of 5.3%, subjects with hip OA had a
significantly increased risk of fracture (vertebral or on-vertebral) [odds
ratio (OR) 2.38, 95% CI 1.06-5.35] compared to controls. Subjects with
lumbar spine OA, however, had a significantly reduced risk of fracture
(OR 0.45, 95% CI 0.23-0.80) compared to controls.
Arden NK et al. Br J Rheumatol 1996; 35: 1299-1304
ROA Knee and Fractures
After adjustment for potential confounding factors, including parameters
of postural stability and BMD, the relative risks for incident vertebral and
non-vertebral fractures in the presence of knee ROA were 2.0
Bergink AP et al. Arthritis Rheum 2003; 49: 648-57
Decreased Prevalence of Vertebral
Fractures Associated With Spine OA
Roux C et al. Ann Rheum Dis 2008; 67: 224-8
Previous OP Fracture is Protective Against
Development of Knee Osteophytes
Less Development of Knee OA with
Prevalent Vertebral Fracture
Bergink AP et al. Bone 2005; 37: 446-56
The higher BMD in OA patients does not
seem to protect against fracture, apart
from a possible decreased prevalence of
fracture in patients with spine OA.
A previous OP fracture may protect
against the development of knee OA
CLINICAL LINKS BETWEEN
OA AND OP
Falls
Women with ROA Knee and Knee Pain
Fall More
Muraki S et al. Arthritis Care Res 2011; 63: 1425-31
Reduced Falls with ROA Hip
Fractures in Subjects With Knee OA is
Not Related to Falls
Arden NK et al. Arthritis Rheum 2006; 55: 610-5
Is the increased fracture risk in OA related
to more falls?
Risk Factors for OA and OP
Butlink IEM and Lems WF. Curr Rheumatol Rep 2013; 15: 328
Vitamin D Receptor (VDR) Gene
• The VDR has been found in osteoarthritic cartilage
and osteophytes
VDR: AA vs aa of ApaI Polymorphism
and OA
Zhu Z-H et al. Rheumatol (Oxford). 2014 Feb 4
LINKS BETWEEN OA AND
VITAMIN D
According to this study,
Almost Two Thirds of Postmenopausal
Women With OP Have Vitamin D Inadequacy*
In a cross-sectional observational international study
in 2589 postmenopausal women with osteoporosis
90
N=2589
Prevalence (%)
80
63.9%
70
60
48.7%
50
40
30.8%
30
14.3%
20
10
2.8%
0
<9
<15
<20
<25
<30
Cutoff points for 25(OH)D concentration (ng/ml)
*Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/ml
Study Design: Observational, cross-sectional study of 2589 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D
distribution.
Adapted from Lips P et al. Poster presented at ASBMR, Nashville, TN, USA, September 23–27, 2005; Heaney RP Osteoporos Int 2000;11:553–555.
25(OH)D and BMD in Older Japanese
Women
Femoral Neck
R2=0.020, P=0.003
Lumbar Spine
Nakamura K et al. Bone 2008; 42: 271-7
Effect of Vitamin D and Calcium
Supplementation on Risk of Falling
• 122 women
Reduction in falls
• Age: 63–99 years
1.2
• Randomized, double-blind,
1.0
controlled trial
• Calcium 1200 mg/day
+ vitamin D 800 IU/day
0.8
Fall risk
• Calcium 1200 mg/day
–49%
0.6
• 12-week duration
0.4
• Mean serum 25(OH)D
0.2
12 ng/ml at baseline
• Women living in long-term
care units
p=0.01
0.0
Calcium
only
(n=44)
Calcium +
vitamin D
(n=45)
Adapted from Bischoff HA et al J Bone Miner Res 2003;18:343–351.
Risk of Hip
Fracture
Stratified by
Vitamin D
Intake
Bischoff-Ferrari HA et al. N
Engl J Med 2012; 367: 40-9
Effects of Vitamin D on Cartilage/Pain
• Vitamin D has been shown to stimulate synthesis of
proteoglycan by mature articular chondrocytes in tissue culture
• Vitamin D has been shown to modulate the activity of
metalloproteinase (MMP) enzymes that degrade cartilage. Low
levels of 24,25- and 1,25-vitamin D increase MMP activity in
vitro, and normal levels reduce MMP activity
• Low serum levels of 25-vitamin D may alter the balance of
articular cartilage metabolism by increasing the production of
degradative enzymes and decreasing the synthesis of
proteoglycan matrix proteins, leading to cartilage loss
• The active metabolite 1,25(OH)2D has an anti-proliferative
effect and downregulates inflammatory markers, which are
associated with change in non-weightbearing knee pain
Lane NE et al. Arthritis Rheum 1999; 42: 854-60
Laslett LL et al. Ann Rheum Dis 2014; 73: 697-703
25(OH)D: Incident or Worsening Knee Pain
25(OH)D: Incident or Worsening Hip Pain
Laslett LL et al. Ann Rheum Dis 2014; 73: 697-703
Vitamin D and Cartilage Volume
Longitudinally, baseline serum 25(OH)D level predicted change in both
medial and lateral tibial cartilage volume (β = +0.04% per annum per nmol/l
for both; p < 0.05), and change in serum 25(OH)D level was positively
associated with change in medial tibial cartilage volume.
Ding C et al. Arthritis Rheum 2009; 60: 1381-9
25(OH)D: Progression Knee OA
McAlindon TE et al. Ann Intern Med 1996; 125: 353-9
Vitamin D and Knee OA Progression
Felson DT et al. Arthritis Rheum 2007; 56: 129-36
25(OH)D: Progression of ROA Knee
18%
Tertiles of
serum
25(OH)D
levels:
mean & range,
nmol/l
16%
14%
12%
10%
39 (15-50)
62 (51-74)
98 (75-188)
8%
6%
4%
2%
0%
Progressive ROA
Bergink AP et al. J Clin Rheumatol 2009; 15: 230-7
25(OH)D: Incident Hip OA (JSN)
25
Tertiles of
serum
25(OH)D
(ng/ml)
20
15
Lowest (8-22)
Middle (23-39)
Highest (30-72)
10
5
0
No. Hips With Incident OA
Lane NE et al. Arthritis Rheum 1999; 42: 854-60
Vitamin D Supplementation on OA Pain
McAlindon T et al. JAMA 2013; 309: 155-62
Vitamin D Supplements on OA Knee
Structure
McAlindon T et al. JAMA 2013; 309: 155-62
PATHOPHYSIOLOGY OF OA
AND OP LEADING TO
TREATMENT OPTIONS
Bone Remodeling Sequence
Bone Turnover in OA
• Bone marrow lesions (BMLs)
are areas of micro-fractures in
of trabecular bone, with
various stages of healing
associated with fibrous
replacement of bone marrow
and increased activation of
BMUs i.e. high bone
remodeling
• BMLs are associated with
pain and radiographic
progression
• There is also increased bone
remodeling in subchondral
bone (up to 20-fold higher)
Bone Marrow Lesions (BMLs) and Knee
OA Progression
Relationship between BMLs at baseline and annual percentage
cartilage volume loss over 2 years
Relationship between BMLs at baseline and knee joint
replacement over 4 years (n = 16)
Increasing severity of BMLs at baseline was associated with a 57% increased risk (95% CI 4, 135; P =
0.03) of having a knee joint replacement over 4 years when adjusted for age, gender and K–L grade
Tanamas SK et al. Rheumatol 2010; 49: 2413-9
Bone Loss is Related to Cartilage Loss
• In the multivariable models, a BMD loss of 0.1 gm/cm2
was associated with cartilage volume loss of 1.25% per
year (p=0.02)
Lee JY et al. Arthritis Rheum 2013; 65: 1541-6
Risedronate Suppresses Bone Resorption
Spector TD et al. Arthritis Res Ther 2005; 7: R625-R633
Patient Global Assessment
Risedronate and Knee OA Symptoms
• In terms of detectable progression (i.e. loss of JSW ≥ 25% or ≥
0.75 mm), change from baseline values in JSW at 1 year
showed a greater presence of detectable progression in the
placebo (8%) and risedronate (5 mg) (4%) (p = 0.36) groups
than in the risedronate (15 mg) group (1%) (p = 0.067)
Spector TD et al. Arthritis Res Ther 2005; 7: R625-R633
Risedronate Does Not Reduce Knee OA
Progression
Multinational Knee OA Study
Bingham III CO et al. Arthritis Rheum 2006; 54: 3494-507
Effect of IV Zoledronate on OA Knee
Effect on Pain
Effect on Bone Marrow Lesions
Laslett LL et al. Ann Rheum Dis 2012; 71: 1322-8
Meta-Analysis of Oral Bisphosphonates
on OA Pain
Davis AJ et al. PloS One 2013; 8(9): e72714
Strontium: Reduction in Lumbar Spine
ROA Progression
Bruyere O et al. Ann Rheum Dis 2008; 67: 335-9
SEKOIA: Strontium in Knee OA
Reginster J-Y et al. Ann
Rheum Dis 2013; 72: 179-86
Oral bisphosphonates do not reduce OA
progression. Strontium seems promising
but its usage will be limited by CV
concerns
Conclusions
• OA and OP are not mutually exclusive; despite
slightly higher BMD in OA patients, they are
still at risk of OP fractures
• Patients with a previous OP fracture and high
levels of 25(OH)D may have less incident OA
• Drugs that modify (subchondral) bone
remodeling may be the future DMOADs
Thank
you!

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