slide 1 dr mampedi bogoshi osteoporosis † trademark of merck & co., inc., whitehouse station,...
TRANSCRIPT
Slide 1
Dr Mampedi Bogoshi
Osteoporosis
†Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA
Slide 2
Discussion Points
Osteoporosis Burden of Disease
Risk Factors
Vitamin D and Calcium
Recommendations and management
Slide 3
Bone development
Peak bone mass between 25 and 35.
Bones thicken
Bones are at their strongest
From 35 to menopause bone mass slowly declines.
Gradually your body starts to lose more bone than it makes.
Slide 4
Osteoporosis
Burden of Disease
Slide 5
What is Osteoporosis?
“….a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture”
Slide 6
Risk factors for osteoporosis: Age Low Oestrogen Women are at a greater risk than men, Thin or have a small frame White or Asian race
Women who are postmenopausal, including those who have had early or surgically induced menopause
Cigarette smoking, Eating disorders such as anorexia nervosa or bulimia, low amounts of calcium
in the diet, Heavy alcohol consumption, Inactive lifestyle, Certain medications, e.g. corticosteroids and anticonvulsants
Rheumatoid arthritis itself is a risk factor for osteoporosis. Family History
Slide 7
Fracture Risk and Bone Quality
Bone quality may be defined as the ability of bone to resist fracture
Changes in the rate of bone turnover can affect mineralization, microarchitecture, and bone mass – Changes in key properties of bone can lead to
alterations in bone strength and the ability of bone to resist fractures
The primary goal in treating osteoporosis should be fracture prevention
Adapted from Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement. 2000;17(1):1–45; Miller PD et al J Clin Densitom 1992;2(3):323–342; Boivin GY et al Bone 2000;27(5):687–694; Dempster DW Osteoporos Int 2002;13(5):349–352.
Slide 8
Bone Quality
4 bone properties affect bone strength:
1) BMD
2) Bone Turnover
3) Bone Microarchitecture
4) Bone Mineralisation
Slide 9
How Key Properties of Bone Affect Fracture Risk
Altersmicroarchitecture and
bone mineralization
Adapted from Garnero P et al J Bone Miner Res 1996;11(3):337–349; Miller PD et al J Clin Densitom 1999;2(3):323–342; Boivin GY et al Bone 2000;27(5):687–694.
BMD
BoneTurnover
BoneStrength
FractureRisk
Slide 10
1) Bone Quality
Slide 11
Bone Turnover Bone turnover (remodeling) is a continuous process of bone
resorption followed by bone formation– Measured noninvasively by assessing biochemical markers
of bone remodeling e.g. ALP
Higher bone turnover has been shown to be linked to increased
rates of bone loss and increased risk of fracture– Patients with higher* bone turnover were 4.1 times more likely
to suffer a fracture
Greater decreases in bone turnover are associated with lower risk of fracture**
CTx=C-telopeptide of type I collagen; NTx=N-telopeptide of type I collagen
*In a clinical study to evaluate markers of bone turnover as predictors of hip fracture in elderly women followed for 22 months**In a meta-analysis of 18 clinical trials of antiresorptive therapy to examine the association between BMD and risk of nonvertebral fractures
Adapted from Kanis JA. Pathogenesis of osteoporosis and fracture. In: Osteoporosis. Malden: Blackwell Science, Inc., 1996:22–55; Miller PD et al J Clin Densitom 1999;2(3):323–342; Garnero P et al J Bone Miner Res 1996;11(10):1531–1538; Hochberg MC et al J Clin Endocrinol Metab 2002;87(4):1586–1592.
Slide 12
2) BMD
Slide 13
How Key Properties of Bone Affect Fracture Risk
BoneStrength
FractureRisk
BoneTurnover
Altersmicroarchitecture and
bone mineralization
BMD
Slide 14
Bone Mineral Density
BMD measurement is a noninvasive technique used to establish or confirm a diagnosis of osteoporosis and provide an assessment of fracture risk– 1 SD decrease in BMD has been shown to correlate
with 1.5- to 2-fold increases in fracture risk
>80% of bone strength was related to BMD in two separate in vitro studies*
*Two separate cadaveric studies of correlation between BMD and strength of the proximal femur and BMD and thoracic vertebral strength in elderly patients
Adapted from National Osteoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 2003; Cummings SR et al Lancet 1993;341(8837):72–75; Bouxsein ML et al Bone 1999;25(1):49–54; Moro M et al Calcif Tissue Int 1995;56(3):206–209.
Slide 15
Decreased BMD In Vivo Has Been Associated with Fracture Incidence
In a meta-analysis, the link between low BMD and fracture risk was similar to or stronger than– Diastolic blood pressure
and stroke– Serum cholesterol
and coronary disease
Evaluation of relationship between bone mineral content of four skeletal sites to the incidence of vertebral fracture over six years in 699 postmenopausal women
Meta-analysis of prospective cohort studies from 1985 to 1994 containing data on baseline BMD and fracture follow-up to determine whether BMD would predict fracture
Adapted from Miller PD et al Calcif Tissue Int 1996;58(4):207–214; Wasnich RD et al J Nucl Med 1989;30(7):1166–1171; Marshall D et al BMJ 1996;312(7041):1254–1259.
Prospective Cohort Study
0
10
30
60
Inci
den
ce o
f fr
actu
res
(fra
ctu
res
per
100
0 p
atie
nt-
year
s)
50
40
20
2 SD 1 SD Mean –2 SD–1 SD
Bone mass
SpineDistal radiusCalcaneus
Slide 16
Increases in BMD Lead to Greater Bone Strength In Vitro
Laboratory studies to determine correlation between BMD and bone strength in human cadaveric specimens
Adapted from Bouxsein ML et al Bone 1999;25(1):49–54; Moro M et al Calcif Tissue Int 1995;56(3):206–209.
Test set-up to determine bone strength
Two Separate Laboratory Studies
0
0
6000
8000
Fem
ora
l fa
ilu
re l
oad
(N
)
Trochanteric BMD (g/cm2)
r2=0.92p<0.0001
2000
4000
0.2 0.4 0.6 0.8 1.0 0
0
5000
6000
T11
fai
lure
lo
ad (
N)
Lumbar spine (lateral) BMD (g/cm2)
r2=0.88p<0.001
2000
4000
0.25 0.50 1.00 1.25 1.50
3000
1000
0.75
Schematic ofmaterial testingsystem tobreak vertebra
Slide 17
3) Microarchitecture
Slide 18
How Key Properties of Bone Affect Fracture Risk
BoneStrength
FractureRisk
BoneTurnover
Altersmicroarchitecture and
bone mineralization
BMD
Slide 19
Microarchitectural Changes in Osteoporosis Over Time
Trabecular Bone
Bone volume
Trabecular thickness
Trabecular number
Horizontal struts
Connectivity
Plate perforation
Cortical Bone
Cortical porosity
Cortical thickness
Slide 20
Trabecular Bone Microarchitecture
Bone microarchitecture is assessed invasively to determine the bone’s structural parameters
Excessive bone resorption alters trabecular architecture and increases cortical porosity
By normalizing turnover, it may be possible to preserve bone microstructure and decrease cortical porosity
Adapted from Thomsen JS et al Bone 2002;30(1): 267–274; Dempster DW Osteoporos Int 2002;13(5):349–352; Bell KL et al Bone 2000;27(2):297–304; Riggs BL, Melton LJ III J Bone Miner Res 2002;17(1):11–14; Boivin GY et al Bone 2000;27(5):687–694; Masarachia P et al. Posters presented at the 2003 American Society for Bone and Mineral Research meeting, Minneapolis, Minnesota, September 19–23, 2003; Roschger P et al Bone 2001;29(2):185–191.
Slide 21
Assessing Trabecular Bone Microarchitecture
Iliac crest bone biopsy is an invasive procedure used to obtain bone samples from humans
Bone biopsy samples are used for evaluating trabecular microarchitecture by 2-D and (3D) micro-CT imagery
Trabecular microarchitecture changes have not been established to be predictive of fracture risk
Adapted from Thomsen JS et al Bone 2002;30(1):267–274.
Slide 22
Overall Limitations of Iliac Crest Biopsy Iliac crest is not an osteoporotic fracture site
Histomorphometric parameters vary even at contiguous sites in the iliac crest– Intersample variation of bone volume from two contiguous
sites was 15.7% in one study (n=55 patients)*
Histomorphometric parameters at the iliac crest correlate poorly with those at the spine and hip
*Evaluation of intersample variation for an individual and for patient groups in two contiguous transiliac crest samples in 55 patients (mean age 55 years);
Adapted from Chavassieux PM et al Calcif Tissue Int 1985;37(4):345–350; Thomsen JS et al Bone 2002;30(1):267–274.
Slide 23
Slide 24
Slide 25
Consequences of Osteoporosis
Clinically, osteoporosis manifests in occurrence of characteristic low-trauma fractures, the best documented of these being hip, vertebral, and distal forearm fractures.
Source: The burden of musculoskeletal conditions at the start of the new millennium: a report of a WHO scientific group. WHO Technical Report Series 919, World Health Organization, Geneva 2003.
Slide 26
Slide 27Source: Zimmerman SI et al. The prevalence of osteoporosis in nursing home residents. Osteoporosis Int 1999;9:151-77.
Epidemiology of Osteoporosis
Osteoporosis is known to increase with age.
Osteoporosis is more prevalent in women than men.
63.5%71.1%
85.8%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
65-74 75-84 85+
Age
Prevalence of osteoporosis for white female nursing home residents:
Slide 28
Source: Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. World Health Organ Tech Rep Ser 2003;919:i-x, 1-218, back cover.
Increasing Risk of Osteoporotic Fracture in Women, by Age
Slide 29Source: US Congress of Health Technology Assessment 1994, OTA-BP-H-120. US Government Printing Office, Washington DC.
0%
10%
20%
30%
40%
50%
50-64 65-74 75-84 85+
All Hip Fx Male Hip Fx Female Hip Fx
An
nua
l Mor
talit
y R
ate
Hip Fracture Mortality
Slide 30
Vitamin D: Its Importance in the Treatment
of Osteoporosis
Slide 31
The Importance of Vitamin D
Vitamin D is essential for ensuring intestinal absorption of calcium
Lack of vitamin D leads to increased release of PTH and bone resorption
Evidence suggests that vitamin D inadequacy increases risk of fracture
Vitamin D inadequacy also increases the risk of falls
PTH=parathyroid hormone
Adapted from Parfitt AM et al. Am J Clin Nutr. 1982;36:1014–1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273–278; Lips P et al. J Clin Endocrinol Metab. 2001;86:1212–1221; LeBoff MS et al. JAMA. 1999;281:1505–1511; Bischoff HA et al. J Bone Miner Res. 2003;18:343–351; Gallacher et al. Curr Med Res Opin. 2005;21:1355–1361.
Slide 32
Vitamin D Production
25(OH)D=25-hydroxyvitamin D; PTH=parathyroid hormone; 1,25(OH)2D=1,25-dihydroxyvitamin D
Adapted from Holick MF. Osteoporos Int. 1998;8(suppl 2):S24–S29.
Skin
Liver
Kidney
DietVitamin D3
Vitamin D2
Intestine
Bone
ProD3 PreD3 Vitamin D3
25(OH)D
1,25(OH)2D
PTH (+)
UVBSun
(+) Low PO2–
4
Increase calcium and phosphorus absorption
Mobilize calcium stores
Maintain serum calcium and phosphorus
Metabolic functions Bone health Neuromuscular functions
Slide 33
Sources of Vitamin D
Sunlight exposure– Major source of vitamin D, providing the majority of the body’s daily
requirement– Vitamin D production is affected by season, duration of exposure,
sunscreen use, and skin pigmentation Endogenous production
– Ability of skin, liver, and kidneys to form and process vitamin D Dietary intake
– Minor source of vitamin D– Vitamin D is rare in foods other than fatty fish, eggs, and supplemented
dairy products*– Even vitamin D–fortified dairy products may not contain level indicated
on label– Vitamin D can be supplied by multivitamins and supplements– Supplements containing vitamin D alone are not readily available– Patient compliance with supplementation therapy is inconsistent
*Sold in the United States, Canada, Argentina (optional), Brazil, Guatemala, Honduras, Mexico, Philippines (optional), and Venezuela
Adapted from Holick MF; Allain TJ, Dhesi J; Webb AR et al; Parfitt et al; Matsuoka LY et al; Holick MF; Lips P; Macleod CC et al; Omdahl JL et al; Chen TC et al; Holick MF et al; Heaney RP; Segal E et al; Webb AR et al; Faulkner H et al; Roche Vitamins Europe Ltd.
Slide 34
Recommendations for Vitamin D Intake
Europe
The Scientific Committee for Food of the Commission of the EuropeanCommunities recommends 400 IU of vitamin D daily for the elderly (age 65)
United States
The Institute of Medicine has defined adequate daily intake of vitamin Daccording to age Adults up to age 50 200 IU Adults 51–70 400 IU Adults >70 600 IU
No toxic effects were reported in 48 of 50 adults with vitamin D deficiency given a single intramuscular dose of 600,000 IU annually in a clinical study to assessthe efficacy and tolerability profile of high vitamin D intake.
Adapted from European Commission. Report on Osteoporosis in the European Community: Action on Prevention. Luxembourg: Office for Official Publications of the European Communities, 1998; Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: Institute of Medicine, National Academy Press, 1997; Diamond TH et al. Med J Aust. 2005;183:10–12.
Slide 35
Appropriateneuromuscular
function
Appropriateneuromuscular
function
Vitamin D Inadequacy* Has Important Consequences
*Vitamin D inadequacy is defined as serum 25(OH)D <30 ng/mL.
Adapted from Parfitt AM et al. Am J Clin Nutr. 1982;36:1014–1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273–278; Holick MF. Osteoporos Int. 1998;8(suppl 2):S24–S29; DeLuca HF. Metabolism. 1990;39(suppl 1):3–9; Lips P. In: Advances in Nutritional Research. New York, Plenum Press, 1994:151–165; Pfeifer M et al. Trends Endocrinol Metab. 1999;10:417–420; Heaney RP. Osteoporos Int. 2000;11:553–555.
Bone mineraldensity
Bone mineraldensity
Parathyroidhormone
Parathyroidhormone
Calcium absorptionCalcium
absorption
Risk of fractureRisk of fracture
Artist rendition
Slide 36
Vitamin D Is Essential for Calcium Absorption
Calcium absorptiona
Pretreated with vitamin Db
(n=24)
Not pretreated with vitamin Dc
(n=22)aP<0.001bSerum vitamin D 32 ng/mLcSerum vitamin D 20 ng/mL
Adapted from Heaney RP et al. J Am Coll Nutr. 2003;22:142–146.
0
1
2
3
4
5+65%
AU
C (
mgh
r/L
)
Results of 2 randomized, crossover studies conducted approximately 1 year apart in 34 postmenopausal women
Slide 37
Vitamin D Supplementation Decreased Fracture Risk
5-year randomized, double-blind, controlled trial
N=2686
Age 65 to 85 years
Vitamin D = 100,000 IU once every 4 months (equivalent to 800 IU/day)
Adapted from Trivedi D et al. BMJ. 2003;326:469.
Fra
ctu
re r
elat
ive
risk
(hip
, wri
st, f
ore
arm
, sp
ine)
–33%
Untreated(n=1341)
Treated(n=1345)
P=0.02
0.0
0.2
0.4
0.6
0.8
1.0
1.2
In a clinical study,
Slide 38
Effect of Vitamin D and Calcium Supplementation on Risk of Falling 122 women
Age: 63 to 99 years
Randomized, double-blind, controlled trial– Calcium 1200 mg/day– Calcium 1200 mg/day
+ vitamin D 800 IU/day
12-week duration
Mean serum 25(OH)D 12 ng/mL at baseline
Adapted from Bischoff HA et al. J Bone Miner Res. 2003;18:343–351.
Calcium only
(n=44)
Calcium + vitamin D
(n=45)
Fal
l ris
k
0.0
0.2
0.4
0.6
0.8
1.0
1.2
–49%
Reduction in falls
P=0.01
Slide 39
*Vitamin D inadequacy was defined as serum 25(OH)D <30 ng/mL.
Study Design: Cross-sectional, international study of 2589 community-dwelling women with osteoporosis from 18 countries to evaluate serum 25(OH)D distribution
Adapted from Lips P et al. J Intern Med. In press.
Pre
vale
nce
(%
)
0
10
30
40
60
80
90
Regions
N=2589
50
70
20
81.8%
MiddleEast
53.4%
71.4%
AsiaAll LatinAmerica
63.9%
Australia
60.3%
Europe
57.7%
In a cross-sectional, international study in postmenopausal women with osteoporosis
A High Prevalence of Vitamin D Inadequacy* Was Seen Across All Geographic Regions
According to a recent study,
Slide 40
Reasons for High Prevalence of Vitamin D Inadequacy in Postmenopausal Women
Lack of sunlight exposure, including women who use sunscreen
Vitamin D is not common in the diet
Ability to synthesize vitamin D in the skin decreases with age
Lack of compliance taking daily supplements
Adapted from Marcus R. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill Medical Publishing Division, 2001:1715–1743; Bringhurst FR. In: Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill Medical Publishing, 2005:2238–2249; Matsuoka LY. J Clin Endocrinol Metab. 1987;64:1165–1168; Parfitt AM. Am J Clin Nutr. 1982;36:1014–1031; Allain TJ, Dhesi J. Gerontology. 2003;49:273–278; Holick MF et al. Lancet. 1989;2:1104–1105; MacLaughlin J, Holick MF. J Clin Invest. 1985;76:1536–1538; Resch H et al. Poster presented at: ECCEO; March 15–18, 2006; Vienna, Austria; Gaugris S et al. Poster presented at: ECTS and IBMS; June 25–29, 2005; Geneva, Switzerland; Hanley DA et al. Poster presented at: ECCEO; March 15–18, 2006; Vienna, Austria.
Slide 41
Low Patient Compliance With Vitamin D Supplements
Fewer than 1 in 5 women with osteoporosis take vitamin D supplementationa
33% of patients are taking supplements containing vitamin D onlyb
In Austria, where calcium and vitamin D supplementation are free to patients– 73% of patients take calcium and vitamin D combination
supplements – 20% of patients take supplementation regularly
aIn France, the United Kingdom, and GermanybIn the United Kingdom and Mexico
Adapted from Gaugris S et al. Poster presented at: ECTS and IBMS; June 25–29, 2005; Geneva, Switzerland; Resch H et al. Poster presented at: ECCEO; March 15–18, 2006; Vienna, Austria.
Slide 42
Summary of the Importance of Vitamin D in the Treatment of Osteoporosis
Vitamin D is essential for calcium absorption
Postmenopausal women have difficulty getting enough Vitamin D
Vitamin D inadequacy is widespread in postmenopausal women
Vitamin D supplementation has been shown to reduce the risk of fracture and falls
Adapted from Parfitt AM et al. Am J Clin Nutr. 1982;36:1014–1031; Gaugris S et al. QJM. 2005;98:667–676; Bettica P et al. Osteoporos Int. 1999;9:226–229; Lips P et al. J Clin Endocrinol Metab. 2001;86:1212–1221; Lips P et al. J Intern Med. In press; Trivedi DP et al. BMJ. 2003;326:469; Bischoff HA et al. J Bone Miner Res. 2003;18:343–351.
Slide 43
Bone turnover
The properties of bone quality are unfavorably altered by increased bone turnover. The consequences of increased bone turnover associated with osteoporosis can include:– Decreased bone mass– Decreased mineralization– Increased porosity– Disrupted architecture/trabecular connectivity
Biochemical markers are valuable tools in research investigations because they measure bone turnover. They are not commonly used in clinical practice for the treatment and management of osteoporosis.
Slide 44
Slide 45
Daily Calcium Needs
11-24 years old 1200-1500mg
25 years-menopause 1000mg
After menopause
Not on oestrogen 1500mg
On oestrogen 1500mg
>65 yrs old 1000mg
Slide 46
Dairy
Source Calcium per serving
Non fat milk 302 mg per cup
Low fat yoghurt 300 mg/cup
Low fat milk 297 mg/cup
Ice Cream 176 mg/cup
Cottage cheese 155 mg/cup
Fish and Beans
Sardines (canned with bones) 371 mg/3 oz
Salmon (canned with bones) 167 mg/3 oz
Slide 47
Nutrition facts
Packaged foods have a labels
Calcium supplements
Vitamin D = 400IU of vitamin D daily
(milk, multivitamins and sunshine)
Slide 48
Keeping your bones strong
Protein rich or salty foods
medications
inactivity
smoking
Slide 49
Stay active
Resistance exercises
Weight bearing
Vary activities