Transcript Diabete e osteoporosi

Diabetes and osteoporosis
Stefania Maggi
CNR Center on Aging, Padua, Italy
MGSD
Istanbul, April 26-29, 2007
Projected Trend
70
60
Estimated prevalence of
diabetes (1.000.000)
50
3250
80
1995
1998
2025
40
30
20
10
0
1950 2050
629
378
Africa America Mediter. Europe Sud-east West Pacific
Asia
area
1950 2050
600
0
400
742
668
10
1950 2050
1950 2050
Estimated no of hip fractures: (1000s)
Adapted from Cooper C et al, Osteoporosis Int, 1992;2:285-289
High risk factors for low bone mass-related fractures
(risk > 2)
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Aging (> 70-80 years)
Low body weight
Weight loss
Physical inactivity
Corticosteroids
Anticonvulsivants
Primary hyperparathyroidism
Anorexia nervosa
Gastrectomy
Pernicious anemia
Prior osteoporotic fracture
Diabetes Mellitus type 1
Espallargues, Osteoporosis Int 2001
Moderate risk factors for low bone mass-related fractures
(1< risk < 2)
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Gender (female)
Smoking (active)
Low sunlight exposure
Family history of osteoporotic fracture
Surgical or early menopause
Short fertile period, late menarche, no lactation
Low calcium intake
Hyperparathyroidism
Hyperthyroidism
Rheumatoid arthritis
Diabetes Mellitus type 2
Espallargues, Osteoporosis Int 2001
Diabetes Mellitus: Health Impact of the Disease
6th leading cause of
death
Renal
failure*
Blindness*
Life expectancy
5 to 10 yr
Diabetes
Cardiovascular
disease 2X to 4X
Nerve damage in
60% to 70% of patients
Amputation*
OSTEOPOROSIS
*Diabetes
is the no. 1 cause of renal failure, new cases of blindness,
Diabetes Statistics., 2000
and nontraumatic amputations
Risk factors for osteoporotic fractures in diabetes
Risk for osteoporosis
•Poor glycemic control
•Nephropathy
•Neuropathy
•Diabetic diarrhea
Risks for falls
Due to diseases associated with diabetes
•Grave’s disease
•Celiac sprue
•Amenorrhea
•Delayed puberty
•Eating disorders
• Hypoglycemia
• Nocturia
• Poor vision
• Poor balance
• Orthostatic hypotension
• Impaired joint motility
Brown & Sharpless, Clinical diabetes, 2004
The Iowa Women’s Health Study
• Prospective cohort study of 41,836
postmenopausal women, started in 1985
• Questionnaire on history of diseases and
Risk factors
• Average follow up of about 12 years
Nicodemus et al.,Diabetes care, 2001
Adjusted RR for hip fracture in postmenopausal
women, stratified by type of diabetes
Hip fracture
Type 1 diabetes
Type 2 diabetes
12.25
(5.05-29.7)
1.70
(1.21-2.38)
Adjusted for age, smoking, estrogen use, BMI, waist/ hip ratio
(Nicodemus et al.,Diabetes care, 2001)
Study for Osteoporotic fractures
(SOF)
• Prospective cohort study of osteoporosis
and fracture in 9.704 women 65+
• Questionnaire on history of diseases and
Risk factors+ clinical visit + BMD
• Average follow up of about 9 years
Schwartz, J Clin Endocrinol Metab, 2001
Adjusted RR for fracture in older diabetic
women (N=657), stratified by insulin use
(Schwartz et al, J Clin Endocrinol Met., 2001)
Diabetic women
not using insulin
Hip
Proximal humerus
All nonvertebral
Fractures
Foot
Diabetic women
using insulin
1.82
1.14
(1.24-2.69)
(0.42-3.08)
1.94
2.38
(1.24-3.02)
(0.97-5.81)
1.30
1.39
(1.10-1.53)
(0.97-1.98)
1.09
2.68
(0.64-1.84)
(1.18-6.06)
Adjusted for age, family history, smoking, estrogen use, BMI, physical functioning, peripheral
neuropathy, drugs’ use, falls
Despite having a higher bone density,
on average, the women with diabetes
had a higher risk of hip and proximal
humerus fractures. Other factors,
associated with frailty and fracture,
including falls, (and chronic
complications of diabetes) did not
account for the association between
diabetes and fracture.
•Schwartz, J Clin Endocrinol Metab, 2001
Bone Mineral Density (BMD) at the hip in subjects with
diabetes type 1, diabetes type 2 and without diabetes
1
P<0.05
P<0.005
0,9
0,8
0,7
0,6
Type 1
Type 2
Controls
0,5
0,4
0,3
0,2
0,1
0
Men
Women
Tuominen et al, Diabetes Care, 1999
Is diabetes
associated
with a
decrease in
bone strength
that is not
reflected in
the
measurement
of BMD?
Model for the effects of diabetes on BMD
at different times of life
Krakauer et al, Diabetes, 1995
Association with diabetes type 1:
high rates of bone turnover
Secondary
Hyperparathyroidism
Hypomagnesemia
Increased bone resorption
Decreased
1-25 Hydroxycholecalciferol
Decreased bone formation
Decreased IGF-I
and Insulin
Association with diabetes type 2:
low rates of bone turnover
Bone formation
Peripheral
insulin
resistance
Hyperinsulinemia
Impaired
glucose
tolerance
Defective glucorecognition
Decrease bone resorption
Early diabetes
b-cell failure
Late diabetes
Rosato et al, Calcif Tissue Int, 1998
A model of the interaction between Type 2 DM
and bone quality impairment
Increased AGE-modified protein
(nonenzymatic glycosylation)
AGE-modified collagen
AGE on bone matrix
impairment in the secretion of
cytokines and insulin-like growth factor
alteration in the activities
of collagen and bone cells
sarcopenia
(McCarthy et al,Acta diabetol, 2001)
Sarcopenia
• Age-related decline in
muscle mass
• Result
– Slow walking speed
– Low physical activity
– Decreased exercise
tolerance
– Low grip strength
– Increased fall rates
– Decreased bone strength
• Both males and females
have age-related decline
in muscle mass
• Sarcopenia affects
women more
– Lower baseline total
muscle mass
– Increased rate of loss of
muscle mass in
postmenopausal period
• Thus, women reach
critical threshold of
muscle mass loss and
weakness more quickly
Young men
Cortical area: 319 mmq
Total area: 372 mmq
Old men
Cortical area: 333 mmq
Total area: 432 mmq
Aging
Young woman
Cortical area: 289 mmq
Total area: 341 mmq
Old woman
Cortical area: 230 mmq
Total area: 353 mmq
Figure 3. Age-related differences in cortical and total bone area in men
and woman. Participants of the InCHIANTI study
Has Fat a Protective Role for the Skeleton?
“Pros & Cons”
Rosen CJ et al. Nature, 2006
Bone Cells Formation
Rosen JC et al. Nature Clinical Practice, 2006
Bone Homeostasis
Modified by Pei L et al. JCI, 2004
Bone Is a Target For The Antidiabetic Compound
Rosiglitazone
Control
Rosiglitazone
Rzonca SO et al. Endocrinology, 2004
Thiazolidinedione Use and Bone Loss in Older
Diabetic Adults
Schwartz AV et al. JCEM, 2006
Conclusions
The presence of osteoporosis in a diabetic patient is
often not considered, but the risk of fragility
fractures is higher.
Besides optimal glycemic control, general
recommendations regarding adequate dietary
calcium and Vit.D intake, regular exercise,
adequate treatment for diabetes and avoidance of
other potential risk factors should be given.