steroid-induced osteoporosis: “first, do no harm” · steroid-induced osteoporosis: “first, do...
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Steroid-Induced Osteoporosis:
“First, Do No Harm”
Karen E. Hansen, M.D.Assistant Professor of Medicine
Rheumatology SectionUniversity of WI
This CME program is sponsored by an unrestricted educational grant from Proctor & Gamble
Hippocrates, Father of Medicine
• I will neither give deadly drug to anybody who asks for it, nor will I make a suggestion to this effect.
Learning Objectives
1. Understand the prevalence of steroid use in clinical practice
2. Recall the adverse effects of steroids on bone
3. List treatment options for steroid induced osteoporosis
Who takes steroids?
• Over 5.5 million prescriptions issued by general practitioners in the United Kingdom in 1993
• An estimated 1% of adult Americans take steroids
• Among 65,786 patients in one large practice, continuous use of steroids was recorded in
– 0.5% of people ages 12-94 years– 1.7% of women age > 55 years
Walsh, BMJ 1996; 313:344-6
Prevalence of CIO
• Most common form of drug-related osteoporosis• Most common form of secondary osteoporosis in
both men and women• Between 30-50% of people taking steroids > 3
months experience fragility fractures– Vertebrae or ribs– Pelvis– Other sites
Caplan, J R Soc Med 1994;87:200-202Tannenbaum, J Clin Endocrinol Metab 2002;87:4431-37Johnson, Arch Int Med 1989;149:1069-1072
Emphysema and Asthma
CIO and Chronic Obstructive Pulmonary Disease
*P<0.05 vs. ISU or NSU; **P<0.005 vs ISU. McEvoy CE, et al, 1998.
**
*
010
2030
4050
6070
Systemicsteroid users
(n=125)
Never steroid users
(n=117)
Inhaledsteroid users
(n=70)
Perc
ent
(%)
At least one vertebralfractureMultiple vertebralfractures (>2)Severe vertebralfractures
Rheumatoid Arthritis
Risk Factors for Bone Loss in RA
• 1110 patients with RA from five centers
• All patients enrolled in ARAMIS
• Questionnaire regarding fractures over past 13 years, and risk factors for fracture
• 50 variables investigated in univariate analysis, comparing 226 cases with fracture to the remaining controls
• Multivariate analysis with stepwise logistic regression to determine most important risk factors for fracture
Michel, J Rheumatol 1993;20:1666-9
Prednisone is the Most Important Risk Factor for Fracture in RA
• 7% increased risk of fracture per year of prednisone use
• Use for > 5 years was associated with a fracture rate of 33%
Michel, J Rheumatol 1993;20:1666-9
Is the Treatment Worse than the Disease?
• Obesity
• Diabetes
• Hypertension
• Mood Changes, Insomnia
• Cataracts, Glaucoma
• Infection
• Muscle Weakness
• Skin fragility
• Gastritis
• Avascular Necrosis
Osteoporosis
30-50 % of patients on chronic steroid therapy sustain osteoporotic fractures
Osteoporosis is not a benign disease,
particularly when compounded with another chronic disease.
BaselineBaseline One Year LaterOne Year Later
70 Year-Old Woman With Newly Diagnosed Temporal Arteritis
Complications of Osteoporosis
• Pain• Height loss• Kyphosis• Activity limitations• Constipation and other
abdominal symptoms• Psychological symptoms• Another fracture• Restrictive lung disease
The Consequences of Fracture
• Morbidity: pain, fear, limited mobility
• Mortality: one in four with hip fracture die within the following year
• Money: the financial cost of treating osteoporotic fractures is estimated at $10-15 billion annually
NIH Consensus Statement on Osteoporosis, 2000
http://consensus.nih.gov/cons/111/111_statement.htm#introduction
Gold, Bone 1996;18(S3):185-189
Mechanisms by Which Steroids Harm Bone
Cardinal Histologic Features ofSteroid-Induced Osteoporosis
Decreased bone formation rate
Decreased trabecular wall thickness
Decreased osteoblast function
In situ death of portions of bone
Manolagas, JBMR 1999;14:1061-1066
Bone Remodeling Cycle
11 22
33 44
With SteroidsWith Steroids
Manolagas SC. JBMR 1999;14:1063.
11 22
33 44
NormalNormal
OsteoclastOsteoclast OsteoblastOsteoblast
Decreased Osteoblast number
Premature osteoblast apoptosis
Incomplete repairof bone
Treatment with steroids causes:
• three fold increase in osteoblast apoptosis
• dramatically increased osteocyte apoptosis
• early increase in osteoclastic bone resorption
Manolagas, J Clin Invest 1998;102:274-282
Other Potential Contributing Factors that Lead to Bone Loss with Steroids
1. Sex Steroid Deficiency
2. Defective vitamin D metabolism with secondary hyperparathyroidism
3. Hypercalciuria
4. Underlying disease
5. Immobility related to underlying disease
Adler, Arch Intern Med 2003;163:2619-2624
Laan R, Ann Intern Med 1993;119:966.
00 2020 4444
44
22
00
--22
--44
--66
--88
--1010
% ChangeLumbar Trabecular
Bone Mineral Density(BMD)
Placebo(n = 17)
Prednisone(n = 13)
WeeksWeeks
Rapid BMD Decline Due to Glucocorticoidsin Rheumatoid Arthritis
Cessation of steroids
Fracture Risk with Steroids
• Retrospective cohort study using UK General Practice Research Database
• Controls matched to steroid users for age, gender
• 244,235 steroid users and 244,235 controls
• Mean age 57 years, 59% female
• Most frequent indication for steroids: respiratory disease (40%)
Van Staa TP, JBMR 2000;15:993-1000
Fracture Risk During Steroid Therapy
0.99
1.77 2.271.55
2.59
5.18
0
1
2
3
4
5
6
Relative Risk
Hip Vertebral Fractures
< 2.5 mg2.5-7.5 mg> 7.5 mg
Van Staa TP, JBMR 2000;15:993-1000
Relative Risk of Fracture after Cessation of Steroids
020406080
100120140160180
Year 1 Year 2
Non
vert
ebra
l Fra
ctur
es
> 10 grams> 6 months
Suggests osteoblast recovery
Fracture Risk and Dose of Corticosteroids
Relative risk of fracture by dosages of prednisolone, van Staa TP, et al, 1998.
0
1
2
3
4
5
6
2.5 mg/d 2.5-7.5 mg/d >7.5 mg/d
Rel
ativ
e ris
k of
frac
ture
co
mpa
red
with
con
trol
Hip fractureVertebral fracture
Fracture Rates in Subjects with and without Steroid Use
05
10152025303540
-4 -3.5 -3 -2.5 -2 -1.5 -1
T-score
Perc
ent w
ith F
ract
ure
ControlsSteroid Users
Van Staa, Arthritis Rheum 2003;48(11):3224-3229
NormalNormalTrabecularTrabecularBoneBone
GIOPGIOPGIOPGIOP
BreakageBreakageof of TrabeculaeTrabeculae
GeneralizedGeneralizedThinningThinning
of of TrabeculaeTrabeculae
Overview of GIOP
– Initial rapid bone loss withinthe first months
– Trabecular (spine) bone preferentiallyaffected
– Bone loss may partially reverse withcessation of steroid
Who is at Risk for GIOP ?
– Both men and women
– Older adults more likely to fracture since baseline bone mass may be closer to fracture threshold
– Underlying steroid-requiring disease may also increase bone loss and/or fracture risk
Physician Perception Regarding Toxicity: rank the importance of 11 side effects of steroids
0102030405060708090
OP DM
Weight
Mood
Sleep
Muscle
Skin
65 yo woman45 year old woman45 year old man
Buckley, J Rheumatol 1998;25:2195-202
Do Physicians Treat CIO?
0102030405060708090
100Ha
rring
ton
Wal
sh
Peat
Receiving Treatment
PERCENT
Initial Clinical Work-Up of Steroid Induced Osteoporosis
Risk factors for bone loss
Physical exam
Laboratories
Bone density test
Guidelines for BMD Measurement
• Baseline BMD prior to/within 6 months of initiating therapy
• Follow-up every 6 months until bone mass shows no decline, then annually thereafter
• Be sure to measure spine bone mass, since loss of trabecular (vertebral) bone is more rapid
ISCD Guidelines, J Clin Densitom
Diagnosis of CIO: Biochemical Assessment
• 25-hydroxyvitamin D• Intact PTH• 24-hour urinary calcium• Testosterone, FSH, LH
• Complete blood count• creatinine• calcium• alkaline phosphatase• liver enzyme• phosphorus
Treatment
Management of CIO: Goals of Treatment
Prevent bone loss
Reduce fracture risk
Alleviate pain associated with existing fracture(s)
Maintain/increase muscle strength
Initiate lifestyle changes as needed
Vitamin D
Meta-Analysis of Randomized, Controlled Trials Using Vitamin D
• 10: Change in Lumbar Spine BMD at 12 months
• 20: Fracture Rates
• Pooled analysis of vitamin D and calcium versus no therapy or calcium only
• Pooled analysis of vitamin D with/without calcium versus bisphosphonate / calcitonin / flouride
Amin, Arthritis Rheum 1999;42(8):1740-1751
Vitamin D versus Calcium or No therapy
• 11 studies comprising 560 subjects
• 9 compared vitamin D with calcium to calcium only (n=5) or no therapy (n=4)
• Vitamin D doses range from 400 IU daily to 100,000 IU weekly
Amin, Arthritis Rheum 1999;42(8):1740-1751
Vitamin D versus Calcium or No therapy
• Pooled effect size of vitamin D plus calcium was 0.60 (CI 0.34-0.85) with a 3.2% increase in spine BMD
• Pooled effect size of vitamin D alone was 0.57 (CI 0.36-0.78)
• Fracture rates did not reach statistical significance, pooled effect size –0.89 (p=0.08)
Amin, Arthritis Rheum 1999;42(8):1740-1751
Meta-Analysis of Vitamin D for GIOPComparisons to No Rx/Calcium
WaradyWarady 19941994
Adachi 1996Adachi 1996
Buckley 1996Buckley 1996
TalalajTalalaj 19961996
BijlsmaBijlsma 19881988
SambrookSambrook 19931993
EmkeyEmkey 19941994
SambrookSambrook 19971997
ReginsterReginster 19991999
Pooled EffectPooled Effect
--1.51.5 --11 --0.50.5 00 0.50.5 11 1.51.5 22 2.52.5FavorsFavors Effect SizeEffect Size FavorsFavors
No Therapy/Calcium AloneNo Therapy/Calcium Alone Vitamin D Plus CalciumVitamin D Plus Calcium
Vs. no therapyVs. calcium alonePooled Effect
AminAmin S. et al. S. et al. Arthritis Rheum.Arthritis Rheum. 1999;42:17401999;42:1740--51.51.
Hormone Replacement Therapy
HRT Increases Spine Bone Density Among Steroid Users
• 200 women with RA, including 21% on steroids
• Mean daily prednisone dose of ~7 mg
• Randomized to estradiol 50 μg patch or calcium 400 mg
• BMD of spine and hip at baseline, 12 and 24 months
• High withdrawal rate during study (26.5%)
• Steroid group analyzed separately, lower body weight and baseline bone mass in steroid users (p<0.05)
Hall GM, Arthritis Rheum 1994;10:1499-1505
66
22
00
--44
--6600 1212 2424
--22
44
% C
han
ge%
Cha
nge
Fem
oral
BM
DFe
mor
al B
MD
MonthsMonths
CalciumCalcium
HRTHRT(n = 17)(n = 17)
(n = 15)(n = 15)
Hall, Arthritis Rheum 1994;37:1499–1505
% C
han
ge%
Cha
nge
Lum
bar
BM
DLu
mba
r B
MD
Estrogen for GIOP Prevention
--6600 1212 2424
66
22
00
--44
--22
44(n = 18)(n = 18)
(n = 16)(n = 16)
CalciumCalcium
HRTHRT
MonthsMonths
No fractures in either group
P<0.05 P=ns
Testosterone Therapy
• 15 asthmatic men on long-term steroids with low serum testosterone
• Randomized to 12 months of IM testosterone 250 mg monthly or placebo
• Cross over to opposite therapy at 12 months, with 4 month “wash out” for those initially on testosterone
• One gram calcium for all subjects
• BMD every 4 months
Reid, Arch Intern Med 1996;156:1173-77
Testosterone Replacement Therapy in the Treatment of CIO
p=0.005 vs. baseline BMD; p=0.05 between-group difference Reid, Arch Intern Med 1996;156:1173-77
-5.0
-2.5
0.0
2.5
5.0
Testosterone Control
Cha
nges
in lu
mba
r spi
ne B
MD
(%)
at 1
yea
r
Calcitonin
A Comparison of Calcium, Calcitriol, and Calcitonin
• 103 patients starting long-term steroids randomized to one year of:
– Calcium, calcitriol, and calcitonin nasal spray 400 IU – Calcium and calcitriol 0.5-1.0 mg– Calcium 1,000 mg
• BMD every 4 months
• Spine radiographs at baseline, 1 and 2 years
Sambrook, NEJM 1993;328:1747
Calcitonin Maintains Spine Bone Mass
-5
-4
-3
-2
-1
0
1Pe
rcen
t Cha
nge
Spine FemoralNeck
Spine FemoralNeck
Calcium, Calcitriol,CalcitoninCalcium, Calcitriol
Calcium
One year Two years
P ns for difference between groups 1 and 2
P< 0.05 for difference between groups 1 and 2
Nasal Calcitonin Prevents Steroid Induced OP
• 31 subjects with PMR initiating prednisone > 10 mg daily
• Randomized to nasal calcitonin 100 IU or placebo nasal spray
• Calcium 800 mg daily
• Randomization stratified for age, sex, initial BMD, and initial steroid dose
• Primary outcome by ITT analysis: change in spine BMD at 12 months
Adachi, Brit J Rheumatol 1997;36:255-259
Calcitonin Prevents Bone Loss
-7-6
-5-4
-3-2
-10
Months
Perc
ent C
hang
e in
Spi
ne
BM
DCalcitonin Placebo
3 120 6
Adachi, Brit J Rheumatol 1997;36:255
Bisphosphonates: Cellular Action
Osteoclasts OsteoblastsBP
BP
Haemopoieticprecursors
BP
Osteoclastrecruitment
Alendronate for the Prevention and Treatment of Steroid Induced OP
• 477 patients taking > 7.5 mg prednisone daily
• Randomized to placebo or 5 or 10 mg of alendronate
• All subjects were given calcium 800-1000 mg and vitamin D 250-500 IU daily
• 48 week study
• Radiographs and BMD at baseline and 48 weeks
Saag, N Eng J Med 1998;339:292-9
Efficacy of Alendronate in Increasing BMD
*P <0.001 vs. control; **P <0.01 vs. control; †P <0.001 vs. baseline, ‡P <0.01 vs. baseline;Saag KG, et al, 1998.
-1.5
-0.5
0.5
1.5
2.5
3.5
Lumbar spine Femoral neck Trochanter Total bodyCha
nge
in B
MD
from
bas
elin
e (%
)at
48
wee
ksControl Alendronate 5 mg Alendronate 10 mg
* †
* †
* ‡ * ‡
‡
* * ‡
* †
* * †
Efficacy of Alendronate: Two Years Follow-Up
-4-3-2-101234
Lumbar spine Femoral neck Trochanter
Cha
nge
in B
MD
from
bas
elin
e (%
)
Control Alendronate 5 mg Alendronate 10 mg Alendronate 2.5 mg year 1, 10 mg year 2
*P<0.001 vs. control; **P<0.01 vs. control; †P<0.05 vs. control. Saag KG, et al, 1998.
**
** **
†
†
Reduction in Fractures with Alendronate
2.3
3.7
00.5
11.5
22.5
33.5
4
Perc
ent
48 weeks
New Fractures
AledronatePlacebo
Saag, N Eng J Med 1998;339:292-9
Risedronate Prevents Steroid Induced Bone Loss
• 228 patients
• Ages 18-85 years old
• Onset of > 7.5 mg of prednisone daily within past 3 months, with expected duration of > 12 months
• Double-blind, placebo-controlled trial using 5 mg risedronate daily
• Calcium 500 mg daily
• Vitamin D < 500 IU daily for those with deficiency
Cohen S, et al. Arthritis & Rheumatism 1999;42(11):2309-2318
-4
-3
-2
-1
0
1
2
3 6 9 12
Time (months)Time (months)
controlrisedronate 5.0 mg
Risedronate Prevents Lumbar Spine Bone Loss
p < 0 .05 vs (*) baseline and (†) control
Mea
n %
Mea
n %
chan
ge fr
om b
asel
ine
chan
ge fr
om b
asel
ine
*† †
*
* *
*
† †
Cohen S, et al. Arthritis & Rheumatism 1999;42(11):2309-2318
17 % havevertebralfracture
6 % have vertebral fracture
-4
-3
-2
-1
0
1
2
3 6 9 12
Time (months)Time (months)
control risedronate 5.0 mg
Risedronate Prevents Femoral Neck Bone Loss
p < 0 .05 vs (*) baseline and (†) control
Mea
n %
Mea
n %
chan
ge fr
om b
asel
ine
chan
ge fr
om b
asel
ine
*† †
*
*
*
†
Cohen S, et al. Arthritis & Rheumatism 1999;42(11):2309-2318
Risedronate Increases Bone Mass in Subjects Already on Long-Term Steroids
• 290 men and women ages 18-85 years
• Prednisone > 7.5 mg daily for > 6 months
• Randomized to– risedronate 2.5 or 5 mg daily– placebo
• Calcium 1 gram, vitamin D 500 IU daily
• 12 month study with primary endpoint: change in lumbar spine bone density
Reid, JBMR 2000;15:1006-1013
% C
hang
e Fr
om
Bas
elin
e (±
SEM
)
–2
–1
0
1
2
3
4 * †
* †*
Risedronate Increases BMD in Patients on Long-term Glucocorticoid Therapy
Risedronate Increases BMD in Patients on Long-term Glucocorticoid Therapy
*p≤0.05 vs baseline; †p ≤0.05 vs controlReid DM, et al. J Bone Miner Res. 2000;15:1006-1013
Control Risedronate 5 mg
LumbarSpine
FemoralNeck
FemoralTrochanter
Risedronate Reduces Fracture Rates in Patients taking Glucocorticoid Therapy
0
6
12
18
24
Patients ContinuingTreatment
Patients InitiatingTreatment
Combined
Inci
denc
e, o
ne y
ear (
%)
70%
p=0.01
Control Risedronate 5 mg
Absolute risk reduction = 11% (combined)All patients were taking >7.5 mg oral prednisone or equivalentWallach S, et al. Calcif Tissue Int. 2000;67:277-285.
0
5
10
15
20
Pooled control patients Pooled risedronatepatientsPa
tient
s w
ith v
erte
bral
frac
ture
s (%
)
Effect of Risedronate on Vertebral Fracture Rates
Pooled vertebral fracture rates from 518 patients on steroid therapy. *P=0.016 vs. control. Reid D, et al, 1998.
*
70% reduction
Treatment Number of Change in lumbar pooled trials spine BMD (%)*
Vitamin D 18 +1.96
Calcitonin 11 +2.11
Bisphosphonates 18 +5.31†
Bisphosphonates in the Management of CIO: A Meta-Analysis
*Compared with no treatment or with calcium alone†P=0.0001 compared with calcitonin or vitamin D
FDA Approved Treatments for Steroid Induced Osteoporosis
Alendronate (Fosamax)
Risedronate (Actonel)
Intravenous Ibandronate
• 115 men and women• Lumbar spine T-score below -2.5• Steroid therapy continuously for 2 years• Steroid dose > 7.5 mg daily
Ringe, Osteoporos Int 2003;14:801
Intravenous Ibandronate
• Open-label single center trial
• All patients received calcium 500 mg daily
• Patient pairs, matched for baseline characteristics, were assigned to– Daily oral alfacalcidol 1 mcg– IV ibandronate 2 mg every 3 months
Ringe, Osteoporos Int 2003;14:801
Lumbar Bone Mass over 36 Months
02468
10121416
6 12 18 24 36
Months
Mea
n C
hang
e, %
IbandronateAlfacalcidiol
p<0.001
Ibandronate Reduces Rate of New Compression Fracture
0
5
10
15
20
25Pe
rcen
t with
New
Ve
rteb
ral F
ract
ure
36Months
alfacalcidiol ibandronate
p=0.043, 62% reduction
Cyclical Etidronate and Prevention of Corticosteroid-Induced Bone Loss
Roux et al (N=117) Adachi et al (N=141)
*P<0.05 between-group difference Adachi JD, et al, 1997. Roux, J Clin Endocrnol Metab 1998;83:1128-33
**
-4-3-2-1012
Lumbarspine
Femoralneck
Trochanter Lumbarspine
Femoralneck
Trochanter
Cha
nges
in B
MD
from
ba
selin
e (%
) at
1 y
ear Etidronate Control
*
0
2
4
6
Lumbar spine* Femoral neck TrochanterChan
ge in
BM
D fr
om b
asel
ine
(%)
Men Pre-menopausal women Post-menopausal women
Etidronate: Pooled Results from Three Randomized Trials
*P<0.05 between-group difference. Roux C, et al,1998.
Pamidronate
• 32 patients beginning steroids > 10 mg daily for > 3 months
• Randomized to one of three groups– Pamidronate 90 mg iv once plus calcium– Pamidronate 90 mg iv then 30 mg q 3 months plus calcium– Calcium 800 mg once daily
– 9 patients per group with similar baseline characteristics
Boutsen, JBMR 2001;16:104-112
Change in Bone Mass at 12 Months
-5-4-3-2-1012345
Perc
ent C
hang
e
L1-L4
Total H
ipFem
oral N
eck
Troch
anter
Pamidronate 1Pamidronate 3Calcium
**
*
*
* Denotes p <0.05
no new fractures in either group with
radiographs at baseline and 12 months
Parathyroid Hormone for Steroid Induced Osteoporosis
• 51 postmenopausal women with T-score < -2.5
• All taking HRT for at least one year
• All taking prednisone for the past year
• Randomized to PTH or no therapy
• All given calcium 1500 mg daily
• All given 2 multivitamins daily
Lane, J Clin Invest 1998;102:1627-1633
-202468
1012
Perc
ent C
hang
e
L1-L4
Total H
ipNec
k
Troch
anter
Radius
Total H
ip, 24
m
PTH and HRT HRT only
The Premenopausal Woman and Bisphosphonates
• Bisphosphonates cross the placenta in rats
• Bisphosphonates given to pregnant rats decreased post-implantation survival, body weight, and fetal ossification
• Bisphosphonates caused prolonged hypocalcemiaand protracted parturition
• Bisphosphonates given to pregnant rabbits had no adverse outcomes
The Premenopausal Woman and Bisphosphonates
• The terminal half life of alendronate in humans is > 10 years
• Mobilization of calcium from the maternal skeleton is crucial for fetal development
• However, a limited number of pregnancies reported to Merck in patients on alendronate show no adverse effects
• Bisphosphonates are considered “Pregnancy Category C
• Use of bisphosphonates should be considered carefully in pre-menopausal women who may in future become pregnant
Time Points to Begin GIOP Rx
• Primary PreventionAt initiation of glucocorticoid therapy
• Secondary PreventionAfter detection of low BMD, but before fractures
• Tertiary PreventionAfter osteoporosis insufficiency fractures
ACR Task Force on Osteoporosis: Initiating Long-Term (>6 months)
Corticosteroid TherapyBaseline BMD
Calcium, vitamin D supplementationPatient education
Modify other risk factorsT score < -1Initiate bisphosphonates
2nd line- consider calcitonin
T score > -1
6-12 months follow-up:Repeat BMD
Decrease >5%: change/add medicationStable or increased: no change in therapy
American College of Rheumatology Task Force on Osteoporosis Guidelines, 2001
Calcium and Vitamin DConsider bisphosphonate to prevent OP
Repeat DXA in 6-12 months
If Hypogonadal,Consider HRT
What shall I do if the duration of steroids is uncertain?
• The US Preventive Task Force recommends screening DXA for all women > 65 years old, and for women between age 60-65 who have low body weight or do not take estrogens
• The ISCD recommends that men receive a screening DXA at age 70
• A DXA will be paid for if a patient is taking steroids, has suffered a low-trauma fracture, or has a dorsal kyphosis
First, Do No Harm
Any patient on steroids
presents an
opportunity to perform
primary, secondary or tertiary
treatment of
steroid induced bone loss
Lumbar Spine
% C
han
ge%
Ch
ange
From
Bas
elin
eFr
om B
asel
ine
at 2
4 M
onth
sat
24
Mon
ths
22
11
00
--11
--22
--33
--44TrochanterFemoral
Neck
Buckley LM et al. Ann Intern Med. 1996;125:961–968.* * PP < 0.005< 0.005****PP < 0.025< 0.025
* **
Calcium Plus Vitamin D3
Calcium + D (n = 47)Calcium + D (n = 47)Placebo (n = 49)Placebo (n = 49)
Adapted from Adachi JD. Semin Arth Rheum. 1993;22:377.
↓ OsteoblasticBone Formation
OSTEOPOROSIS
↓ ↓ FSH InducedFSH InducedSex HormoneSex Hormone
ProductionProduction
↓ ↓ LH ResponseLH Responseto LHRHto LHRH
↓ ↓ Sex Hormone Sex Hormone
↓ ↓ CalciumCalcium
↑ ↑ PTHPTH
↓ ↓ G.I. CalciumG.I. CalciumAbsorptionAbsorption
↑ ↑ Urinary CalciumUrinary CalciumExcretionExcretion
Glucocorticoids
↑ OsteoclasticBone Resorption
EstrogenEstrogenTestosteroneTestosterone
Anabolic AgentsAnabolic Agents
CalciumCalciumVitamin DVitamin D ThiazidesThiazides
BisphosphonatesBisphosphonatesCalcitoninCalcitonin
The Effects of Inhaled and Oral Steroids on Bone Mass in Asthmatics
Lumbar Spine BMD
Change
Low Dose Inhaled Steroid
0.916 0.914 g -0.001
High Dose Inhaled Steroid
0.848 g 0.835 g -0.016
< 2.5 Steroid Tapers yearly
0.917 0.925 0.010
> 2.5 Steroid Tapers yearly
0.844 0.802 -0.047
Matsumoto, Chest 2001;120:1468-1473